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Lipodystrophy - childhood onset v4.47 BLM Achchuthan Shanmugasundram Classified gene: BLM as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.47 BLM Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with severe insulin resistance and hence it can be promoted to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.47 BLM Achchuthan Shanmugasundram Gene: blm has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.46 BLM Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: BLM.
Tag Q3_23_NHS_review tag was added to gene: BLM.
Lipodystrophy - childhood onset v4.46 BLM Achchuthan Shanmugasundram Publications for gene: BLM were set to 7585968; 16763388; 21536711; 27710244; 2823277; 2947793
Lipodystrophy - childhood onset v4.45 BLM Achchuthan Shanmugasundram edited their review of gene: BLM: Changed publications to: 7585968, 16763388, 21536711, 27710244, 28232778, 29477938
Lipodystrophy - childhood onset v4.45 BLM Achchuthan Shanmugasundram edited their review of gene: BLM: Changed publications to: 7585968, 16763388, 21536711, 27710244, 28232778, 2947793
Lipodystrophy - childhood onset v4.45 BLM Achchuthan Shanmugasundram Publications for gene: BLM were set to 7585968; 16763388; 2153671; 27710244; 2823277; 2947793
Lipodystrophy - childhood onset v4.44 BLM Achchuthan Shanmugasundram edited their review of gene: BLM: Changed publications to: 7585968, 16763388, 21536711, 27710244, 2823277, 2947793
Lipodystrophy - childhood onset v4.44 BLM Achchuthan Shanmugasundram Publications for gene: BLM were set to
Lipodystrophy - childhood onset v4.43 BLM Achchuthan Shanmugasundram Phenotypes for gene: BLM were changed from Bloom Syndrome, severe insulin resistance to Bloom syndrome, OMIM:210900; Insulin resistance, HP:0000855
Lipodystrophy - childhood onset v4.42 BLM Achchuthan Shanmugasundram edited their review of gene: BLM: Added comment: Insulin resistance was observed in six individuals and lipid profile abnormalities were reported in five of ten individuals with Bloom syndrome (PMID:16763388).; Changed rating: GREEN; Changed publications to: 7585968, 16763388, 2153671, 27710244, 2823277, 2947793
Lipodystrophy - childhood onset v4.42 PSMA3 Achchuthan Shanmugasundram Classified gene: PSMA3 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.42 PSMA3 Achchuthan Shanmugasundram Gene: psma3 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.41 PSMA3 Achchuthan Shanmugasundram Publications for gene: PSMA3 were set to
Lipodystrophy - childhood onset v4.40 PSMA3 Achchuthan Shanmugasundram Tag digenic tag was added to gene: PSMA3.
Lipodystrophy - childhood onset v4.40 PSMA3 Achchuthan Shanmugasundram changed review comment from: PMID:26524591 - Two unrelated cases with heterozygous variants in PSMA3 and PSMB8 were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:26524591 - Two unrelated cases with heterozygous variants in PSMA3 and PSMB8 were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.

The 'digenic' tag has been added as both reported cases had variants in PSMB8 in addition to PSMA3 variants.
Lipodystrophy - childhood onset v4.40 PSMA3 Achchuthan Shanmugasundram edited their review of gene: PSMA3: Added comment: PMID:26524591 - Two unrelated cases with heterozygous variants in PSMA3 and PSMB8 were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; Changed rating: AMBER; Changed publications to: 26524591
Lipodystrophy - childhood onset v4.40 PSMA3 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations in PSMB4 or PSMB8 (PMID: 26524591, 34416217) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB8, PMSA3 PMID: 26524591). PSMB9 has also been implicated in digenic cases but this is in a single familes and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9. Only DIGENIC cases of CANDLES involving PSMA3 have been reported.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations in PSMB4 or PSMB8 (PMID: 26524591, 34416217) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB8, PMSA3 PMID: 26524591).

PSMB9 has also been implicated in digenic cases but this is in a single familes and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9. Only DIGENIC cases of CANDLES involving PSMA3 have been reported.
Lipodystrophy - childhood onset v4.40 PSMB8 Achchuthan Shanmugasundram changed review comment from: The 'digenic' tag has been added as there are two cases reported with heterozygous variants from both PSMB4 and PSMB8 in addition to patients with homozygous PSMB8 variants.; to: The 'digenic' tag has been added as there are four digenic cases reported (two cases each with heterozygous variants in PSMA3/ PSMB8 and PSMB4/ PSMB8) in addition to patients with homozygous PSMB8 variants.
Lipodystrophy - childhood onset v4.40 PSMB4 Achchuthan Shanmugasundram changed review comment from: PMID:26524591 - One case with compound heterozygous variants in PSMB4 (monogenic), two cases with heterozygous variants in PSMA3 and PSMB8 (digenic) and two cases with heterozygous variants in PSMB4 and PSMB8 (digenic) were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.

PMID:34416217 - A boy with treatment-resistant cutaneous vasculitis was identified with novel heterozygous variants in PSMB4. This patient developed mild lipodystrophy after the successful second hematopoietic stem cell transplantation (HSCT).

This gene has been associated with PRAAS in OMIM and it includes lipodystrophy as one of the clinical manifestations.; to: PMID:26524591 - One case with compound heterozygous variants in PSMB4 (monogenic), two cases with heterozygous variants in PSMB4 and PSMB8 (digenic) and two cases with heterozygous variants in PSMB4 and PSMB9 (digenic) were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.

PMID:34416217 - A boy with treatment-resistant cutaneous vasculitis was identified with novel heterozygous variants in PSMB4. This patient developed mild lipodystrophy after the successful second hematopoietic stem cell transplantation (HSCT).

This gene has been associated with PRAAS in OMIM and it includes lipodystrophy as one of the clinical manifestations.
Lipodystrophy - childhood onset v4.40 PSMB4 Achchuthan Shanmugasundram commented on gene: PSMB4: The 'digenic' tag has been added as there are four additional cases with heterozygous PSMB4 variants and heterozygous variants in either PSMA3 and PSMB8.
Lipodystrophy - childhood onset v4.40 PSMB4 Achchuthan Shanmugasundram Classified gene: PSMB4 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.40 PSMB4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for the association of biallelic variants in PSMB4 with lipodystrophy (two unrelated cases and supporting functional evidence). Hence, this gene can be promoted to green rating in the next GMS review.
Lipodystrophy - childhood onset v4.40 PSMB4 Achchuthan Shanmugasundram Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.39 PSMB4 Achchuthan Shanmugasundram Tag digenic tag was added to gene: PSMB4.
Tag Q3_23_promote_green tag was added to gene: PSMB4.
Tag Q3_23_NHS_review tag was added to gene: PSMB4.
Lipodystrophy - childhood onset v4.39 PSMB4 Achchuthan Shanmugasundram Phenotypes for gene: PSMB4 were changed from Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome) to ?Proteasome-associated autoinflammatory syndrome 3 and digenic forms, OMIM:617591
Lipodystrophy - childhood onset v4.38 PSMB4 Achchuthan Shanmugasundram Publications for gene: PSMB4 were set to
Lipodystrophy - childhood onset v4.37 PSMB4 Achchuthan Shanmugasundram edited their review of gene: PSMB4: Added comment: PMID:26524591 - One case with compound heterozygous variants in PSMB4 (monogenic), two cases with heterozygous variants in PSMA3 and PSMB8 (digenic) and two cases with heterozygous variants in PSMB4 and PSMB8 (digenic) were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.

PMID:34416217 - A boy with treatment-resistant cutaneous vasculitis was identified with novel heterozygous variants in PSMB4. This patient developed mild lipodystrophy after the successful second hematopoietic stem cell transplantation (HSCT).

This gene has been associated with PRAAS in OMIM and it includes lipodystrophy as one of the clinical manifestations.; Changed rating: GREEN; Changed publications to: 26524591, 34416217
Lipodystrophy - childhood onset v4.37 PSMB4 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations (PMID: 26524591, 34416217) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB8, PMSA3 PMID: 26524591). See panel app reviews for autoinflammatory syndromes. PSMB9 has also been implicated in digenic cases but this is in a single familes and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations (PMID: 26524591, 34416217) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB8, PMSA3 PMID: 26524591). See panel app reviews for autoinflammatory syndromes.

PSMB9 has also been implicated in digenic cases but this is in a single familes and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9.
Lipodystrophy - childhood onset v4.37 PSMB8 Achchuthan Shanmugasundram Classified gene: PSMB8 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.37 PSMB8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for this gene to be promoted to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.37 PSMB8 Achchuthan Shanmugasundram Gene: psmb8 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.36 PSMB8 Achchuthan Shanmugasundram commented on gene: PSMB8: The 'digenic' tag has been added as there are two cases reported with heterozygous variants from both PSMB4 and PSMB8 in addition to patients with homozygous PSMB8 variants.
Lipodystrophy - childhood onset v4.36 PSMB8 Achchuthan Shanmugasundram Phenotypes for gene: PSMB8 were changed from Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome) to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040
Lipodystrophy - childhood onset v4.35 PSMB8 Achchuthan Shanmugasundram Publications for gene: PSMB8 were set to
Lipodystrophy - childhood onset v4.34 PSMB8 Achchuthan Shanmugasundram edited their review of gene: PSMB8: Changed publications to: 20534754, 21129723, 21953331, 26524591
Lipodystrophy - childhood onset v4.34 PSMB8 Achchuthan Shanmugasundram Tag digenic tag was added to gene: PSMB8.
Tag Q3_23_promote_green tag was added to gene: PSMB8.
Tag Q3_23_NHS_review tag was added to gene: PSMB8.
Lipodystrophy - childhood onset v4.34 PSMB8 Achchuthan Shanmugasundram edited their review of gene: PSMB8: Added comment: PMID:21129723 - A homozygous missense variant (c.224C>T/ p.Thr75Met) in PSMB8 gene was identified in affected patients from two different families with an autosomal-recessive autoinflammatory syndrome characterised by joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced lipodystrophy (JMP).

PMID:21953331 - Of nine patients from eight families reported in this publication with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome), four patients were homozygous and two were heterozygous for the previously reported missense variant (c.224C>T), one had no PSMB8 variant and one patient was homozygous for a novel nonsense variant (c.405C>A).

This gene has been associated with relevant phenotypes in OMIM (MIM #256040) and Gene2Phenotype ('definitive' rating in the DD panel for Nakajo syndrome) and lipodystrophy has been included as a part of this phenotype in these resources.; Changed rating: GREEN; Changed publications to: 21129723, 21953331
Lipodystrophy - childhood onset v4.34 PSMB8 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations (PMID: 20534754, 21129723, 21953331) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB4, PSMA3)(PMID: 26524591). PSMB9 has also been implicated in digenic causes but these are in single kindreds and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations (PMID: 20534754, 21129723, 21953331) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB4, PSMA3)(PMID: 26524591).

PSMB9 has also been implicated in digenic causes but these are in single kindreds and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9.
Lipodystrophy - childhood onset v4.34 EPHX1 Achchuthan Shanmugasundram changed review comment from: Two unrelated cases presenting with lipoatrophic diabetes were identified with de novo variants in EPHX1 gene (patient 1: p.Thr333Pro; patient 2: p.Gly430Arg). The disease was characterised by loss of adipose tissue, insulin resistance, and multiple organ dysfunction. Functional analysis showed that these variants protein aggregation within the endoplasmic reticulum and to a loss of its hydrolysis activity. In addition, CRISPR-Cas9-mediated EPHX1 knockout (KO) abolished adipocyte differentiation and decreased insulin response.; to: Two unrelated cases presenting with lipoatrophic diabetes were identified with de novo variants in EPHX1 gene (patient 1: p.Thr333Pro; patient 2: p.Gly430Arg). The disease was characterised by loss of adipose tissue, insulin resistance, and multiple organ dysfunction. Functional analysis showed that these variants protein aggregation within the endoplasmic reticulum and to a loss of its hydrolysis activity. In addition, CRISPR-Cas9-mediated EPHX1 knockout (KO) abolished adipocyte differentiation and decreased insulin response.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Lipodystrophy - childhood onset v4.34 EPHX1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: EPHX1.
Tag Q3_23_NHS_review tag was added to gene: EPHX1.
Lipodystrophy - childhood onset v4.34 EPHX1 Achchuthan Shanmugasundram Classified gene: EPHX1 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.34 EPHX1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (two unrelated cases and functional studies) in support of the association of this gene with lipodystrophy and severe insulin resistance. Hence, this gene can be promoted to green rating in the next GMS review.
Lipodystrophy - childhood onset v4.34 EPHX1 Achchuthan Shanmugasundram Gene: ephx1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.33 EPHX1 Achchuthan Shanmugasundram Phenotypes for gene: EPHX1 were changed from Lipodystrophy, Severe Insulin Resistance to lipodystrophy, MONDO:0006573; Insulin resistance, HP:0000855
Lipodystrophy - childhood onset v4.32 EPHX1 Achchuthan Shanmugasundram Publications for gene: EPHX1 were set to
Lipodystrophy - childhood onset v4.31 EPHX1 Achchuthan Shanmugasundram edited their review of gene: EPHX1: Changed rating: GREEN
Lipodystrophy - childhood onset v4.31 EPHX1 Achchuthan Shanmugasundram edited their review of gene: EPHX1: Added comment: Two unrelated cases presenting with lipoatrophic diabetes were identified with de novo variants in EPHX1 gene (patient 1: p.Thr333Pro; patient 2: p.Gly430Arg). The disease was characterised by loss of adipose tissue, insulin resistance, and multiple organ dysfunction. Functional analysis showed that these variants protein aggregation within the endoplasmic reticulum and to a loss of its hydrolysis activity. In addition, CRISPR-Cas9-mediated EPHX1 knockout (KO) abolished adipocyte differentiation and decreased insulin response.; Changed publications to: 34342583
Lipodystrophy - childhood onset v4.31 EPHX1 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: EPHX1 is an epoxide hydroxylase, highly expressed in liver and adipose tissue. De novo missense mutations (p.Thr333Pro and p.Gly430Arg) in EPHX1 carried in heterozygosity were implicated in a lipoatrophic diabetes syndrome in two unrelated probands (PMID: 34342583). In vitro characterisation demonstrated loss of enzyme activity in these two mutants and localisation studies demonstrated aggregation of the mutant EPHX1 isoforms in the ER, suggestive of a dominant negative mechanism of action. Consistent with a causal role for EPHX1 in the affected probands' syndrome, circulating epoxy fatty acids were found to be elevated. Variants implicated in the described clinical syndrome caused EPHX1 to form oligomeric complexes and aggregate in the ER. As such it is likely that simple loss of function mutations in EPHX1 do not cause this syndrome, and a dominant negative effect of the EPHX1 mutants is likely the causal mechanism. Consistent with this EPHX1 appears to be LOF tolerant (pLI gnomad = 0, https://gnomad.broadinstitute.org/gene/ENSG00000143819); to: This gene was added on recommendation of NHSE Genomic Medicine Service:
EPHX1 is an epoxide hydroxylase, highly expressed in liver and adipose tissue. De novo missense mutations (p.Thr333Pro and p.Gly430Arg) in EPHX1 carried in heterozygosity were implicated in a lipoatrophic diabetes syndrome in two unrelated probands (PMID: 34342583). In vitro characterisation demonstrated loss of enzyme activity in these two mutants and localisation studies demonstrated aggregation of the mutant EPHX1 isoforms in the ER, suggestive of a dominant negative mechanism of action. Consistent with a causal role for EPHX1 in the affected probands' syndrome, circulating epoxy fatty acids were found to be elevated. Variants implicated in the described clinical syndrome caused EPHX1 to form oligomeric complexes and aggregate in the ER. As such it is likely that simple loss of function mutations in EPHX1 do not cause this syndrome, and a dominant negative effect of the EPHX1 mutants is likely the causal mechanism. Consistent with this EPHX1 appears to be LOF tolerant (pLI gnomad = 0, https://gnomad.broadinstitute.org/gene/ENSG00000143819).
Lipodystrophy - childhood onset v4.31 MFN2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: MFN2.
Tag Q3_23_NHS_review tag was added to gene: MFN2.
Lipodystrophy - childhood onset v4.31 MFN2 Achchuthan Shanmugasundram Classified gene: MFN2 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.31 MFN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As recommended by NHS, there is sufficient evidence available for associating this gene with lipomatosis and severe insulin resistance and hence this gene can be promoted to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.31 MFN2 Achchuthan Shanmugasundram Gene: mfn2 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.30 MFN2 Achchuthan Shanmugasundram Publications for gene: MFN2 were set to 26085578; 28414270; 3015806
Lipodystrophy - childhood onset v4.29 MFN2 Achchuthan Shanmugasundram edited their review of gene: MFN2: Changed publications to: 26085578, 28414270, 30158064
Lipodystrophy - childhood onset v4.29 MFN2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: Autosomal recessive variants in this gene have been associated with cephalothoracic lipodystrophy in OMIM (MIM #151800), but not in Gene2Phenotype.
Lipodystrophy - childhood onset v4.29 MFN2 Achchuthan Shanmugasundram Phenotypes for gene: MFN2 were changed from MFN2-associated multiple lipomatosis, lipodystrophy, severe insulin resistance, axonal sensorimotor neuropathy to Lipomatosis, multiple symmetric, with or without peripheral neuropathy, OMIM:151800
Lipodystrophy - childhood onset v4.28 MFN2 Achchuthan Shanmugasundram Publications for gene: MFN2 were set to
Lipodystrophy - childhood onset v4.27 MFN2 Achchuthan Shanmugasundram edited their review of gene: MFN2: Changed rating: GREEN; Changed publications to: 26085578, 28414270, 3015806
Lipodystrophy - childhood onset v4.27 MFN2 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Biallelic R707W mutations or R707W in compound heterozygosity with other loss of function variants cause a complex clinical syndrome consisting of multiple lipomas/upper body adipose tissue overgrowth, concomitant lipoatrophy and the development of severe insulin resistance and its metabolic complications. Affected individuals also have a paucisymptomatic axonal neuropathy. This has now been demonstrated in at least 13 patients from 10 independent families (PMID: 30158064, 28414270, 26085578). It is likely that mitochondrial dysfunction in adipose tissue is crucial to the pathogenesis of this condition but the specific cellular and molecular mechanisms remain to be elucidated.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
Biallelic R707W mutations or R707W in compound heterozygosity with other loss of function variants cause a complex clinical syndrome consisting of multiple lipomas/upper body adipose tissue overgrowth, concomitant lipoatrophy and the development of severe insulin resistance and its metabolic complications. Affected individuals also have a paucisymptomatic axonal neuropathy. This has now been demonstrated in at least 13 patients from 10 independent families (PMID: 30158064, 28414270, 26085578). It is likely that mitochondrial dysfunction in adipose tissue is crucial to the pathogenesis of this condition but the specific cellular and molecular mechanisms remain to be elucidated.
Lipodystrophy - childhood onset v4.27 POC1A Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: POC1A.
Tag Q3_23_NHS_review tag was added to gene: POC1A.
Lipodystrophy - childhood onset v4.27 POC1A Achchuthan Shanmugasundram Classified gene: POC1A as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.27 POC1A Achchuthan Shanmugasundram Added comment: Comment on list classification: As recommended by the NHS, there is sufficient evidence (9 unrelated cases) in support of the association of this gene with severe dyslipidaemic insulin resistance. Hence, this gene can be promoted to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.27 POC1A Achchuthan Shanmugasundram Gene: poc1a has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.26 POC1A Achchuthan Shanmugasundram Phenotypes for gene: POC1A were changed from SOFT syndrome, Severe insulin resistance to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, OMIM:614813; Insulin resistance, HP:0000855
Lipodystrophy - childhood onset v4.25 POC1A Achchuthan Shanmugasundram Publications for gene: POC1A were set to
Lipodystrophy - childhood onset v4.24 POC1A Achchuthan Shanmugasundram edited their review of gene: POC1A: Changed publications to: 22440536, 26336158, 28819016, 33372278, 35234134
Lipodystrophy - childhood onset v4.24 POC1A Achchuthan Shanmugasundram edited their review of gene: POC1A: Changed rating: GREEN; Changed publications to: 22440536, 26336158, 28819016,33372278, 35234134
Lipodystrophy - childhood onset v4.24 POC1A Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service:
9 unrelated probands with SHORT syndrome with severe dyslipidaemic insulin resistance are known, this represents 26% of all known cases (PMID: 35234134, 26336158, 28819016, 33372278 ,22440536 see PMID: 35234134 discussion for summary of all published and unpublished cases). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
9 unrelated probands with SHORT syndrome with severe dyslipidaemic insulin resistance are known, this represents 26% of all known cases (PMID: 35234134, 26336158, 28819016, 33372278, 22440536 see PMID: 35234134 discussion for summary of all published and unpublished cases). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.
Lipodystrophy - childhood onset v4.24 POC1A Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: 9 unrelated probands with SHORT syndrome with severe dyslipidaemic insulin resistance are known, this represents 26% of all known cases (PMID: 35234134, 26336158, 28819016, 33372278 ,22440536 see PMID: 35234134 discussion for summary of all published and unpublished cases). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
9 unrelated probands with SHORT syndrome with severe dyslipidaemic insulin resistance are known, this represents 26% of all known cases (PMID: 35234134, 26336158, 28819016, 33372278 ,22440536 see PMID: 35234134 discussion for summary of all published and unpublished cases). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.
Lipodystrophy - childhood onset v4.24 CIDEC Achchuthan Shanmugasundram Phenotypes for gene: CIDEC were changed from Lipodystrophy, familial partial, type 5, 615238 to ?Lipodystrophy, familial partial, type 5, OMIM:615238
Lipodystrophy - childhood onset v4.23 CIDEC Achchuthan Shanmugasundram Classified gene: CIDEC as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.23 CIDEC Achchuthan Shanmugasundram Added comment: Comment on list classification: There is one case with partial lipodystrophy and evidence from mouse models. This gene is already reported in OMIM, but not in Gene2Phenotype. Hence, this gene can only be rated amber with current evidence.
Lipodystrophy - childhood onset v4.23 CIDEC Achchuthan Shanmugasundram Gene: cidec has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.22 CIDEC Achchuthan Shanmugasundram Publications for gene: CIDEC were set to
Lipodystrophy - childhood onset v4.21 CIDEC Achchuthan Shanmugasundram edited their review of gene: CIDEC: Changed rating: AMBER; Changed publications to: 20049731, 25565658, 27710244; Changed phenotypes to: ?Lipodystrophy, familial partial, type 5, OMIM:615238
Lipodystrophy - childhood onset v4.21 PCYT1A Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Compound heterozygous loss of function mutations co-segregate with lipodystrophy and its metabolic sequelae in two independent pedigrees and PCYT1A knockdown impairs adipogenesis in vitro (PMID: 24889630). These patients did not exhibit features of spondylometaphyseal dysplasia or any retinal disesae, despite dedicated assessment. To our knowledge, the basis for the phenotypic heterogeneity in carriers of biallelic loss of function PCYT1A mutations is not understood.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
Compound heterozygous loss of function mutations co-segregate with lipodystrophy and its metabolic sequelae in two independent pedigrees and PCYT1A knockdown impairs adipogenesis in vitro (PMID: 24889630). These patients did not exhibit features of spondylometaphyseal dysplasia or any retinal disesae, despite dedicated assessment. To our knowledge, the basis for the phenotypic heterogeneity in carriers of biallelic loss of function PCYT1A mutations is not understood.
Lipodystrophy - childhood onset v4.21 PCYT1A Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PCYT1A.
Tag Q3_23_NHS_review tag was added to gene: PCYT1A.
Lipodystrophy - childhood onset v4.21 PCYT1A Achchuthan Shanmugasundram Classified gene: PCYT1A as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.21 PCYT1A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (two unrelated cases and functional studies) for promoting this gene to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.21 PCYT1A Achchuthan Shanmugasundram Gene: pcyt1a has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.20 PCYT1A Achchuthan Shanmugasundram edited their review of gene: PCYT1A: Changed rating: GREEN
Lipodystrophy - childhood onset v4.20 PCYT1A Achchuthan Shanmugasundram Phenotypes for gene: PCYT1A were changed from Spondylometaphyseal dysplasia with cone-rod dystrophy, Congenital lipodystrophy to Spondylometaphyseal dysplasia with cone-rod dystrophy, OMIM:608940; congenital generalized lipodystrophy, MONDO:0006536; Insulin resistance, HP:0000855
Lipodystrophy - childhood onset v4.19 PCYT1A Achchuthan Shanmugasundram Publications for gene: PCYT1A were set to
Lipodystrophy - childhood onset v4.18 PCYT1A Achchuthan Shanmugasundram edited their review of gene: PCYT1A: Added comment: Two unrelated patients were identified with biallelic loss-of-function PCYT1A variants (patient 1: p.Glu280del/ p.Val142Met; patient 2: p.Glu280del/ p.333fs) and were reported with lipodystrophy, severe insulin resistance and diabetes. Functional studies showed that the presence of these variants result in near-total lack of PCYT1A expression and significantly reduce PC synthesis via the Kennedy pathway (PMID:24889630). Some of the phenotypes seen in patients such as severe fatty liver and low HDL cholesterol levels have also been seen in the liver-specific deletion of murine PCYT1A gene (PMID:18955728).; Changed publications to: 18955728, 24889630
Lipodystrophy - childhood onset v4.18 PCNT Achchuthan Shanmugasundram Classified gene: PCNT as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.18 PCNT Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promoting this gene to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.18 PCNT Achchuthan Shanmugasundram Gene: pcnt has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.17 PCNT Achchuthan Shanmugasundram Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II, Severe insulin resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Insulin resistance, HP:0000855
Lipodystrophy - childhood onset v4.16 PCNT Achchuthan Shanmugasundram Publications for gene: PCNT were set to
Lipodystrophy - childhood onset v4.15 PCNT Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PCNT.
Tag Q3_23_NHS_review tag was added to gene: PCNT.
Lipodystrophy - childhood onset v4.15 PCNT Achchuthan Shanmugasundram edited their review of gene: PCNT: Added comment: Of 21 patients with biallelic PCNT variants, 18 had insulin resistance, which was severe in the majority of patients. Ten patients had confirmed diabetes (mean age of onset 15 years), and 13 had metabolic dyslipidemia. All patients without insulin resistance were younger than 4 years old. In addition, knockdown of PCNT in adipocytes had no effect on proximal insulin signaling but produced a two-fold impairment in insulin-stimulated glucose uptake, approximately commensurate with an associated defect in cell proliferation and adipogenesis (PMID:21270239).; Changed rating: GREEN; Changed publications to: 21270239
Lipodystrophy - childhood onset v4.15 PCNT Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Severe insulin resistance in the absence of frank lipodystrophy is a common feature of Microcephalic osteodysplastic primordial dwarfism, type II due to PCNT mutations (PMID: 21270239). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
Severe insulin resistance in the absence of frank lipodystrophy is a common feature of Microcephalic osteodysplastic primordial dwarfism, type II due to PCNT mutations (PMID: 21270239). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.
Lipodystrophy - childhood onset v4.15 ALMS1 Achchuthan Shanmugasundram Classified gene: ALMS1 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.15 ALMS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.15 ALMS1 Achchuthan Shanmugasundram Gene: alms1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.14 ALMS1 Achchuthan Shanmugasundram edited their review of gene: ALMS1: Changed phenotypes to: Alstrom syndrome, severe insulin resistance
Lipodystrophy - childhood onset v4.14 ALMS1 Achchuthan Shanmugasundram Phenotypes for gene: ALMS1 were changed from BIALLELIC, autosomal or pseudoautosomal to Alstrom syndrome, OMIM:203800
Lipodystrophy - childhood onset v4.13 ALMS1 Achchuthan Shanmugasundram edited their review of gene: ALMS1: Changed phenotypes to: Almstrom syndrome, severe insulin resistance
Lipodystrophy - childhood onset v4.13 ALMS1 Achchuthan Shanmugasundram Publications for gene: ALMS1 were set to
Lipodystrophy - childhood onset v4.12 ALMS1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ALMS1.
Tag Q3_23_NHS_review tag was added to gene: ALMS1.
Lipodystrophy - childhood onset v4.12 ALMS1 Achchuthan Shanmugasundram edited their review of gene: ALMS1: Added comment: Among 12 unrelated cases with Alstrom syndrome, 10 were identified with ALMS1 variants, of which five had potential founder variant in exon 16. These AS patients had severe early-onset obesity, insulin resistance that increased with age, diabetes, hypertriglyceridemia, and hypertension (PMID:16720663).

Evaluation of 38 patients with AS and matched controls showed that frequent abnormalities include obesity, severe insulin resistance, type 2 diabetes mellitus and adult hypogonadism (PMID:29718281).

This gene has been associated with AS in both OMIM (MIM #203800) and Gene2Phenotype (definitive rating).; Changed rating: GREEN; Changed publications to: 16720663, 29718281, 32958032
Lipodystrophy - childhood onset v4.12 ALMS1 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Severe insulin resistance and its metabolic sequalae are common in Almstrom syndrome (PMID: 32958032, 16720663) which is disproportionate to their adiposity (PMID: 29718281). Along with PCNT and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
Severe insulin resistance and its metabolic sequalae are common in Almstrom syndrome (PMID: 32958032, 16720663) which is disproportionate to their adiposity (PMID: 29718281). Along with PCNT and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.
Lipodystrophy - childhood onset v4.12 BLM Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/174/gene/BLM/#!details), partial lipodystrophy and insulin resistance is a recognised clinical feature of bloom syndrome (PMID: 21536711, 29477938, 16763388) and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244).; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/174/gene/BLM/#!details), partial lipodystrophy and insulin resistance is a recognised clinical feature of bloom syndrome (PMID: 21536711, 29477938, 16763388) and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244).
Lipodystrophy - childhood onset v4.12 WRN Achchuthan Shanmugasundram Classified gene: WRN as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.12 WRN Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases) in support of the association of this gene to severe insulin resistance/ diabetes and partial lipodystrophy and hence can be promoted to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.12 WRN Achchuthan Shanmugasundram Gene: wrn has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.11 WRN Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: WRN.
Tag Q3_23_NHS_review tag was added to gene: WRN.
Lipodystrophy - childhood onset v4.11 WRN Achchuthan Shanmugasundram Phenotypes for gene: WRN were changed from Werner's Syndrome, partial lipodystrophy, severe insulin resistance to Werner syndrome, OMIM:277700
Lipodystrophy - childhood onset v4.10 WRN Achchuthan Shanmugasundram Publications for gene: WRN were set to
Lipodystrophy - childhood onset v4.9 WRN Achchuthan Shanmugasundram edited their review of gene: WRN: Added comment: PMID:22654791 - A homozygous variant (p.Arg732Xaa) in WRN gene has been identified in a 16-year-old female patient with a syndrome comprising short stature, severe insulin resistance, ptosis, and microcephaly.

PMID:23849162 - Biallelic WRN null variants (p.Gln748Xaa homozygous, and compound heterozygous p.Gln1257Xaa/ p.Met1329fs) were identified in two female patients who presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them also had diabetes.

PMID:35780059 - Compound heterozygous variants (c.1290_1293del/ p.Asn430Lysfs*7 & c.2732+5G>A) in WRN gene was identified in a 28 year-old woman who presented with early onset diabetes associated with partial lipodystrophy, severe dyslipidaemia and rapidly progressive liver fibrosis related to non-alcoholic steatohepatitis in the absence of progeroid features.

This gene has been associated with Werner syndrome in both OMIM (MIM #277700) and Gene2Phenotype.; Changed rating: GREEN; Changed publications to: 22654791, 23849162, 27710244, 35780059
Lipodystrophy - childhood onset v4.9 WRN Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Premature insulin resistant diabetes is widely recognised as a complication of Werner's syndrome and lipoatrophy is commonly reported. Crucially - 3 independent pedigrees have now reported lipodystrophy and/or severe insulin resistance as presenting features of Werner's syndrome highlighting that this condition needs to be considered in the differential diagnosis of lipodystrophy (PMID: 22654791, 35780059, 23849162). It has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244).; to: This gene was added on recommendation of NHSE Genomic Medicine Service:
Premature insulin resistant diabetes is widely recognised as a complication of Werner's syndrome and lipoatrophy is commonly reported. Crucially - 3 independent pedigrees have now reported lipodystrophy and/or severe insulin resistance as presenting features of Werner's syndrome highlighting that this condition needs to be considered in the differential diagnosis of lipodystrophy (PMID: 22654791, 35780059, 23849162). It has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244).
Lipodystrophy - childhood onset v4.9 AKT2 Achchuthan Shanmugasundram Classified gene: AKT2 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.9 AKT2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Two unrelated cases and supporting functional evidence from mouse models suggest that this gene can be promoted to green rating in the next GMS review.
Lipodystrophy - childhood onset v4.9 AKT2 Achchuthan Shanmugasundram Gene: akt2 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.8 AKT2 Achchuthan Shanmugasundram Publications for gene: AKT2 were set to 15166380; 17327441
Lipodystrophy - childhood onset v4.7 AKT2 Achchuthan Shanmugasundram Mode of inheritance for gene: AKT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy - childhood onset v4.6 AKT2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: AKT2.
Tag Q3_23_NHS_review tag was added to gene: AKT2.
Lipodystrophy - childhood onset v4.6 AKT2 Achchuthan Shanmugasundram edited their review of gene: AKT2: Added comment: PMID:15166380 - A missense variant (p.Arg274His) in AKT2 gene was identified in a family with autosomal dominant severe insulin resistance, diabetes mellitus and partial lipodystrophy.

PMID:17327441 - Of 94 probands with severe insulin resistance (35 of which had partial lipodystrophy) that were screened for AKT2 variants, one female identified with p.Arg467Trp variant was reported with type 2 diabetes and partial lipodystrophy, while another female identified with p.Arg208Lys variant had severe insulin resistance and acanthosis nigricans. p.Arg467Trp was present in neither 47 ethnically matched control subjects nor in 2 unaffected sons of the carrier. p.Arg208Lys variant was not present in her affected son but was present in 1 of 47 white control subjects.

PMID:12843127 - Functional studies in mice showed that loss of AKT2 results in severe diabetes, age-dependent lipoatrophy and mild growth deficiency.; Changed rating: GREEN; Changed publications to: 12843127, 15166380, 17327441, 27710244
Lipodystrophy - childhood onset v4.6 PIK3R1 Achchuthan Shanmugasundram Classified gene: PIK3R1 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.6 PIK3R1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with lipodystrophy and insulin resistance and hence this gene can be promoted to green rating at the next GMS review.
Lipodystrophy - childhood onset v4.6 PIK3R1 Achchuthan Shanmugasundram Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v4.5 PIK3R1 Achchuthan Shanmugasundram Phenotypes for gene: PIK3R1 were changed from SHORT syndrome, partial lipodystrophy, severe insulin resistance to SHORT syndrome, OMIM:269880
Lipodystrophy - childhood onset v4.4 PIK3R1 Achchuthan Shanmugasundram Publications for gene: PIK3R1 were set to
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_NHS_review tag was added to gene: PIK3R1.
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PIK3R1.
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram edited their review of gene: PIK3R1: Added comment: PMID:23810378 - Nine affected individuals from eight different families were identified with de novo or inherited PIK3R1 variants, including a mutational hotspot (c.1945C>T/ p.Arg649Trp) present in four families. Insulin resistance was present in seven individuals and lipoatrophy was present in 3 individuals.

PMID:26497935 - Clinical reappraisal of detailed phenotypes of 32 individuals with PIK3R1-associated SHORT syndrome showed that IUGR <= 3rd percentile (19/25), postnatal growth retardation (height < -2SD, 25/31), lipoatrophy (26/29), factual dysmorphism (all 32 cases) and insulin resistance (13/17) are the main features of this disease.

PMID:27766312 - Five patients were reported with SHORT syndrome and C-terminal variants in PIK3R1, of which four had extreme insulin resistance without dyslipidemia or hepatic steatosis.

This gene has been associated with relevant phenotypes in both OMIM (MIM #269880) and Gene2Phenotype ('definitive' rating in the DD panel). Both lipoatrophy (lower face, upper limb, buttock) and insulin resistance diabetes has been associated as clinical manifestations of this OMIM phenotype for SHORT syndrome.; Changed rating: GREEN; Changed publications to: 23810378, 26497935, 27710244, 27766312
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service. Below are the comments from NHS:
PanelApp expert review green (https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!), Co-segregates with disease in multiple independent pedigrees (PMID: 27766312, 23810378, 26497935), its gene product is a member of the canonical insulin signalling cascade and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244). SHORT syndrome appears to be caused by C-Terminal mutations affecting the SH2 domain, suggesting a mechanism other than simple loss of function (see Prof Rob Semple's review in Panel app @ https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!); to: This gene was added on recommendation of NHSE Genomic Medicine Service. Below are the comments from NHS:

PanelApp expert review green (https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!), Co-segregates with disease in multiple independent pedigrees (PMID: 27766312, 23810378, 26497935), its gene product is a member of the canonical insulin signalling cascade and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244).

SHORT syndrome appears to be caused by C-Terminal mutations affecting the SH2 domain, suggesting a mechanism other than simple loss of function (see Prof Rob Semple's review in Panel app @ https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!)
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service:
PanelApp expert review green (https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!), Co-segregates with disease in multiple independent pedigrees (PMID: 27766312, 23810378, 26497935), its gene product is a member of the canonical insulin signalling cascade and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244). SHORT syndrome appears to be caused by C-Terminal mutations affecting the SH2 domain, suggesting a mechanism other than simple loss of function (see Prof Rob Semple's review in Panel app @ https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!); to: This gene was added on recommendation of NHSE Genomic Medicine Service. Below are the comments from NHS:
PanelApp expert review green (https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!), Co-segregates with disease in multiple independent pedigrees (PMID: 27766312, 23810378, 26497935), its gene product is a member of the canonical insulin signalling cascade and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244). SHORT syndrome appears to be caused by C-Terminal mutations affecting the SH2 domain, suggesting a mechanism other than simple loss of function (see Prof Rob Semple's review in Panel app @ https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!)
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram changed review comment from: This gene was added on recommendation of NHSE Genomic Medicine Service: Panel app expert review green (https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!), Co-segregates with disease in multiple independent pedigrees (PMID: 27766312, 23810378, 26497935), its gene product is a member of the canonical insulin signalling cascade and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244). SHORT syndrome appears to be caused by C-Terminal mutations affecting the SH2 domain, suggesting a mechanism other than simple loss of function (see Prof Rob Semple's review in Panel app @ https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!); to: This gene was added on recommendation of NHSE Genomic Medicine Service:
PanelApp expert review green (https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!), Co-segregates with disease in multiple independent pedigrees (PMID: 27766312, 23810378, 26497935), its gene product is a member of the canonical insulin signalling cascade and has been endorsed as a cause of lipodystrophy by an international multi-society practice guideline (PMID: 27710244). SHORT syndrome appears to be caused by C-Terminal mutations affecting the SH2 domain, suggesting a mechanism other than simple loss of function (see Prof Rob Semple's review in Panel app @ https://panelapp.genomicsengland.co.uk/panels/174/gene/PIK3R1/#!)
Lipodystrophy - childhood onset v4.3 CIDEC Achchuthan Shanmugasundram reviewed gene: CIDEC: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Familial Partial Lipodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 AKT2 Achchuthan Shanmugasundram reviewed gene: AKT2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe insulin resistance, familial partial lipodystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy - childhood onset v4.3 PSMA3 Achchuthan Shanmugasundram reviewed gene: PSMA3: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 PSMB4 Achchuthan Shanmugasundram reviewed gene: PSMB4: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 PSMB8 Achchuthan Shanmugasundram reviewed gene: PSMB8: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 EPHX1 Achchuthan Shanmugasundram reviewed gene: EPHX1: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: Lipodystrophy, Severe Insulin Resistance; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy - childhood onset v4.3 MFN2 Achchuthan Shanmugasundram reviewed gene: MFN2: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: MFN2-associated multiple lipomatosis, lipodystrophy, severe insulin resistance, axonal sensorimotor neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 POC1A Achchuthan Shanmugasundram reviewed gene: POC1A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: SOFT syndrome, Severe insulin resistance; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 PCYT1A Achchuthan Shanmugasundram reviewed gene: PCYT1A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy, Congenital lipodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 PCNT Achchuthan Shanmugasundram reviewed gene: PCNT: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II, Severe insulin resistance; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 ALMS1 Achchuthan Shanmugasundram reviewed gene: ALMS1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: BIALLELIC, autosomal or pseudoautosomal; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 BLM Achchuthan Shanmugasundram reviewed gene: BLM: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Bloom Syndrome, severe insulin resistance; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 WRN Achchuthan Shanmugasundram reviewed gene: WRN: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Werner's Syndrome, partial lipodystrophy, severe insulin resistance; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.3 PIK3R1 Achchuthan Shanmugasundram reviewed gene: PIK3R1: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: SHORT syndrome, partial lipodystrophy, severe insulin resistance; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy - childhood onset v4.2 PSMA3 Achchuthan Shanmugasundram gene: PSMA3 was added
gene: PSMA3 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: PSMA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSMA3 were set to Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome)
Lipodystrophy - childhood onset v4.2 PSMB4 Achchuthan Shanmugasundram gene: PSMB4 was added
gene: PSMB4 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: PSMB4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSMB4 were set to Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome)
Lipodystrophy - childhood onset v4.2 PSMB8 Achchuthan Shanmugasundram gene: PSMB8 was added
gene: PSMB8 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: PSMB8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSMB8 were set to Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome)
Lipodystrophy - childhood onset v4.2 EPHX1 Achchuthan Shanmugasundram gene: EPHX1 was added
gene: EPHX1 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: EPHX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPHX1 were set to Lipodystrophy, Severe Insulin Resistance
Mode of pathogenicity for gene: EPHX1 was set to Other
Lipodystrophy - childhood onset v4.2 MFN2 Achchuthan Shanmugasundram gene: MFN2 was added
gene: MFN2 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: MFN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MFN2 were set to MFN2-associated multiple lipomatosis, lipodystrophy, severe insulin resistance, axonal sensorimotor neuropathy
Mode of pathogenicity for gene: MFN2 was set to Other
Lipodystrophy - childhood onset v4.2 POC1A Achchuthan Shanmugasundram gene: POC1A was added
gene: POC1A was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: POC1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POC1A were set to SOFT syndrome, Severe insulin resistance
Lipodystrophy - childhood onset v4.2 PCYT1A Achchuthan Shanmugasundram gene: PCYT1A was added
gene: PCYT1A was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: PCYT1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCYT1A were set to Spondylometaphyseal dysplasia with cone-rod dystrophy, Congenital lipodystrophy
Lipodystrophy - childhood onset v4.2 PCNT Achchuthan Shanmugasundram gene: PCNT was added
gene: PCNT was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCNT were set to Microcephalic osteodysplastic primordial dwarfism, type II, Severe insulin resistance
Lipodystrophy - childhood onset v4.2 ALMS1 Achchuthan Shanmugasundram gene: ALMS1 was added
gene: ALMS1 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALMS1 were set to BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy - childhood onset v4.2 BLM Achchuthan Shanmugasundram gene: BLM was added
gene: BLM was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BLM were set to Bloom Syndrome, severe insulin resistance
Lipodystrophy - childhood onset v4.2 WRN Achchuthan Shanmugasundram gene: WRN was added
gene: WRN was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Werner's Syndrome, partial lipodystrophy, severe insulin resistance
Lipodystrophy - childhood onset v4.2 PIK3R1 Achchuthan Shanmugasundram gene: PIK3R1 was added
gene: PIK3R1 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS
Mode of inheritance for gene: PIK3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3R1 were set to SHORT syndrome, partial lipodystrophy, severe insulin resistance
Mode of pathogenicity for gene: PIK3R1 was set to Other
Lipodystrophy - childhood onset v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Lipodystrophy - childhood onset v4.0 Sarah Leigh promoted panel to version 4.0
Lipodystrophy - childhood onset v3.3 FBN1 Catherine Snow Tag Q2_21_rating was removed from gene: FBN1.
Lipodystrophy - childhood onset v3.3 KCNJ6 Catherine Snow Tag Q2_21_rating was removed from gene: KCNJ6.
Lipodystrophy - childhood onset v3.3 OTULIN Catherine Snow Tag Q2_21_rating was removed from gene: OTULIN.
Lipodystrophy - childhood onset v3.3 OTULIN Catherine Snow commented on gene: OTULIN
Lipodystrophy - childhood onset v3.3 KCNJ6 Catherine Snow commented on gene: KCNJ6
Lipodystrophy - childhood onset v3.3 FBN1 Catherine Snow commented on gene: FBN1
Lipodystrophy - childhood onset v3.2 OTULIN Catherine Snow Source Expert Review Green was added to OTULIN.
Source NHS GMS was added to OTULIN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v3.2 KCNJ6 Catherine Snow Source Expert Review Green was added to KCNJ6.
Source NHS GMS was added to KCNJ6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v3.2 FBN1 Catherine Snow Source Expert Review Green was added to FBN1.
Source NHS GMS was added to FBN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Lipodystrophy - childhood onset v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Lipodystrophy - childhood onset v2.23 INSR Ivone Leong commented on gene: INSR
Lipodystrophy - childhood onset v2.22 INSR Ivone Leong gene: INSR was added
gene: INSR was added to Lipodystrophy - childhood onset. Sources: Expert Review Green
Mode of inheritance for gene: INSR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: INSR were set to Diabetes mellitus, insulin-resistant, with acanthosis nigricans, OMIM:610549
Lipodystrophy - childhood onset v2.21 MTX2 Ivone Leong Tag for-review was removed from gene: MTX2.
Lipodystrophy - childhood onset v2.21 MTX2 Ivone Leong commented on gene: MTX2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v2.20 MTX2 Ivone Leong Source Expert Review Green was added to MTX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v2.19 PLIN1 Arina Puzriakova Mode of pathogenicity for gene: PLIN1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Lipodystrophy - childhood onset v2.18 PLIN1 Sarah Leigh edited their review of gene: PLIN1: Added comment: PLIN1 haploinsufficiency is not responsible for the phenotype associated with this gene (PMID:30020498). It would appear that frameshifting variants that escape nonsense-mediated mRNA decay (NMD) are expressed and have a dominant negative effect. At least four frame shifting variants that result in the inclusion of aberrant C-terminal amino acids (125 - 166 amino acids) have been reported in cases of Lipodystrophy, familial partial, type 4 (OMIM:613877) (PMID:21345103;25114292;29747582), together with segregation information in two cases (PMID:21345103). Functional studies show that the variant mRNA is expressed at a lower level than wild type, the variant perilipin was correctly targeted to the lipid-droplet surface, but droplets were smaller than in the wild type cells (PMID:21345103; 25114292).; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Lipodystrophy - childhood onset v2.18 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 25114292; 30020498; 21757733
Lipodystrophy - childhood onset v2.17 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 25114292; 30020498
Lipodystrophy - childhood onset v2.16 BSCL2 Arina Puzriakova Phenotypes for gene: BSCL2 were changed from Lipodystrophy, congenital generalized, type 2, 269700 to Lipodystrophy, congenital generalized, type 2, OMIM:269700; Encephalopathy, progressive, with or without lipodystrophy, OMIM:615924
Lipodystrophy - childhood onset v2.15 OTULIN Ivone Leong Classified gene: OTULIN as Amber List (moderate evidence)
Lipodystrophy - childhood onset v2.15 OTULIN Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Lipodystrophy - childhood onset v2.15 OTULIN Ivone Leong Gene: otulin has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v2.14 OTULIN Ivone Leong Tag Q2_21_rating tag was added to gene: OTULIN.
Lipodystrophy - childhood onset v2.14 KCNJ6 Ivone Leong Classified gene: KCNJ6 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v2.14 KCNJ6 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Lipodystrophy - childhood onset v2.14 KCNJ6 Ivone Leong Gene: kcnj6 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v2.13 KCNJ6 Ivone Leong Tag Q2_21_rating tag was added to gene: KCNJ6.
Lipodystrophy - childhood onset v2.13 FBN1 Ivone Leong Classified gene: FBN1 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v2.13 FBN1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Lipodystrophy - childhood onset v2.13 FBN1 Ivone Leong Gene: fbn1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v2.12 FBN1 Ivone Leong Tag Q2_21_rating tag was added to gene: FBN1.
Lipodystrophy - childhood onset v2.12 OTULIN Ivone Leong Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Lipodystrophy - childhood onset v2.11 FBN1 Ivone Leong Phenotypes for gene: FBN1 were changed from Marfan lipodystrophy syndrome, MIM# 616914 to Marfan lipodystrophy syndrome, OMIM:616914
Lipodystrophy - childhood onset v2.10 KCNJ6 Ivone Leong Phenotypes for gene: KCNJ6 were changed from Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572 to Keppen-Lubinsky syndrome, OMIM:614098; Keppen-Lubinsky syndrome, MONDO:0013572
Lipodystrophy - childhood onset v2.9 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTULIN were set to 27523608; 27559085
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099
Review for gene: OTULIN was set to GREEN
gene: OTULIN was marked as current diagnostic
Added comment: Autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein, leukocytosis, and neutrophilia in the absence of any infection.

At least 3 unrelated families reported.
Sources: Expert Review
Lipodystrophy - childhood onset v2.9 KCNJ6 Zornitza Stark gene: KCNJ6 was added
gene: KCNJ6 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: KCNJ6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ6 were set to 25620207; 29852244
Phenotypes for gene: KCNJ6 were set to Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572
Review for gene: KCNJ6 was set to GREEN
gene: KCNJ6 was marked as current diagnostic
Added comment: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder.
Sources: Expert Review
Lipodystrophy - childhood onset v2.9 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBN1 were set to 20979188; 21594992; 21594993; 24613577; 26860060; 29666143
Phenotypes for gene: FBN1 were set to Marfan lipodystrophy syndrome, MIM# 616914
Review for gene: FBN1 was set to GREEN
gene: FBN1 was marked as current diagnostic
Added comment: The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development.

This specific phenotype is caused by variants occurring in or affecting exon 64.

More than 5 unrelated individuals reported, rabbit model.
Sources: Expert Review
Lipodystrophy - childhood onset v2.9 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900; Partial lipodystrophy to Diabetes mellitus, type II, OMIM:125853; Type 2 diabetes mellitus, MONDO:0005148; Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416; Partial lipodystrophy
Lipodystrophy - childhood onset v2.8 VIM Eleanor Williams gene: VIM was added
gene: VIM was added to Lipodystrophy - childhood onset. Sources: Literature
Mode of inheritance for gene: VIM was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: VIM were set to 32066935
Phenotypes for gene: VIM were set to lipodystrophy HP:0009125
Review for gene: VIM was set to RED
Added comment: Previously variants in this gene have been associated with cataracts (PMID: 26694549, 19126778). Cogne et al 2020 (PMID: 32066935) - report a de novo heterozygous variant in VIM (c.1160 T > C; p.(Leu387Pro)) causing a syndromic disorder affecting craniofacial development, peripheral nervous system, and adipose and ectodermal tissues in a 39 year old male. The variant was identified by WES. Both parents lacked the variant. Expression of human vimentin p.(Leu387Pro) in zebrafish resulted in a phenotype of perturbed body fat distribution, and craniofacial and peripheral nervous system development. Functional studies using patient-derived and transfected cells showed that the variant affects vimentin turnover and its ability to form filaments in the absence of wild-type vimentin.
Sources: Literature
Lipodystrophy - childhood onset v2.7 POLR3GL Ivone Leong Classified gene: POLR3GL as Red List (low evidence)
Lipodystrophy - childhood onset v2.7 POLR3GL Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. There are 3 unrelated families with variants in this gene; however, lipodystrophy is only described in 1 family. Adding as Red gene until further evidence is available.
Lipodystrophy - childhood onset v2.7 POLR3GL Ivone Leong Gene: polr3gl has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v2.6 MTX2 Ivone Leong Tag for-review tag was added to gene: MTX2.
Lipodystrophy - childhood onset v2.6 MTX2 Ivone Leong Classified gene: MTX2 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v2.6 MTX2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to support a gene-disease association. This gene will be rated Amber and promoted to Green at the next review of the panel.
Lipodystrophy - childhood onset v2.6 MTX2 Ivone Leong Gene: mtx2 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v2.5 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Lipodystrophy - childhood onset. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Lipodystrophy - childhood onset v2.5 POLR3GL Zornitza Stark gene: POLR3GL was added
gene: POLR3GL was added to Lipodystrophy - childhood onset. Sources: Literature
Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3GL were set to 31089205; 31695177
Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy
Review for gene: POLR3GL was set to AMBER
Added comment: Biallelic canonical splice variants identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. RNA studies confirmed exon skipping occurs in all affected individuals.

A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD.

Three cases altogether but the phenotypes are very different -- may represent a spectrum with the more severe phenotypes resulting from truncating variants but further cases needed.
Sources: Literature
Lipodystrophy - childhood onset v2.5 Sarah Leigh Panel version has been signed off
Lipodystrophy - childhood onset v2.3 Sarah Leigh Panel version has been signed off
Lipodystrophy - childhood onset v2.0 Ivone Leong promoted panel to version 2.0
Lipodystrophy - childhood onset v1.10 Ivone Leong Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Lipodystrophy - childhood onset v1.8 Ivone Leong List of related panels changed from to R158
Lipodystrophy - childhood onset v1.7 CAV1 Ivone Leong Classified gene: CAV1 as Green List (high evidence)
Lipodystrophy - childhood onset v1.7 CAV1 Ivone Leong Added comment: Comment on list classification: New gene added by reviewer. After reviewing the evidence provided by the expert reviewer, it was decided that there is enough evidence to promote this gene from amber to green.

It should be noted that causative variants might only be those that are either homozygous null variants or heterozygous variants that causes truncated protein to be made.
Lipodystrophy - childhood onset v1.7 CAV1 Ivone Leong Gene: cav1 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v1.6 CAV1 Kevin Colclough commented on gene: CAV1: Id initially classified as green but I think this is more complex due to the fact that there are reports of both dominant and recessively inherited variants causing different phenotypes.I think there is a genotype-phenotype association here, and I dont think haploinsufficiency is a disease mechanism since individuals with heterozygous loss of protein expression do not have a lipodystrophy phenotype (whole gene deletion patients and the heterozygous parents with p.Glu38Ter).All other reported variants are within the last exon and are expected to escape nonsense mediated decay, generating a truncated protein or a full length protein with an altered C-terminal sequence. The p.(Phe160Ter) variant looks to be a definite CGL causing variant. Then there are two other PTC variants resulting in a shorter protein with a lipodystrophy phenotype. And finally two patients with very similar frameshift variants that result in full-length proteins with altered C-terminal amino acid sequence. So it could be that only homozygous null variants or heterozygous variants that result in a truncated protein are causing a lipodystrophy phenotype.
Lipodystrophy - childhood onset v1.5 CAV1 Ivone Leong Phenotypes for gene: CAV1 were changed from ?Lipodystrophy, congenital generalized, type 3, 612526 to ?Lipodystrophy, congenital generalized, type 3, 612526; Lipodystrophy, familial partial, type 7, 606721
Lipodystrophy - childhood onset v1.4 CAV1 Ivone Leong Publications for gene: CAV1 were set to PMID: 18390817; 18237401; 18211975; 25898808; 26176221; 27717241; 11739396; 23049990
Lipodystrophy - childhood onset v1.3 CAV1 Kevin Colclough edited their review of gene: CAV1: Added comment: 5 different loss of function variants have been reported in CAV1 to date associated with a lipodystrophy phenotype. No missense variants reported. GnomAD pLi score of 0.67 does not suggest that CAV1 is intolerant to loss of function variants.

Both heterozygous and homozygous LoF variants have been reported in patients with congenital lipodystrophy (PMID: 18211975, 25898808, 18237401).

A heterozygous c.-88del variant within the 5'UTR was identified in a patient with adult-onset partial lipodystrophy but with no proposed mechanism for a pathogenic effect on CAV1 (PMID: 18237401; the authors incorrectly described this a frameshift variant).

Frameshift variants within the C-terminal region of the gene that are predicted to escape NMD have been reported in patients with PAH but no lipodystrophy phenotype (PMID: 22474227).; Changed publications: PMID: 18390817, 18237401, 18211975, 25898808, 26176221, 22474227, 27717241, 11739396, 23049990; Changed phenotypes: ?Lipodystrophy, congenital generalized, type 3, 612526, Lipodystrophy, familial partial, type 7, 606721
Lipodystrophy - childhood onset v1.3 CAV1 Kevin Colclough gene: CAV1 was added
gene: CAV1 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: CAV1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CAV1 were set to PMID: 18390817; 18237401; 18211975; 25898808; 26176221; 27717241; 11739396; 23049990
Phenotypes for gene: CAV1 were set to ?Lipodystrophy, congenital generalized, type 3, 612526
Penetrance for gene: CAV1 were set to Complete
Review for gene: CAV1 was set to AMBER
gene: CAV1 was marked as current diagnostic
Added comment: Sources: Expert Review
Lipodystrophy - childhood onset v1.2 PLIN1 Sarah Leigh Publications for gene: PLIN1 were set to 21345103; 25114292; 30020498
Lipodystrophy - childhood onset v1.1 PLIN1 Anna de Burca Classified gene: PLIN1 as Green List (high evidence)
Lipodystrophy - childhood onset v1.1 PLIN1 Anna de Burca Gene: plin1 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v1.0 PLIN1 Anna de Burca reviewed gene: PLIN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 30020498; Phenotypes: Lipodystrophy, familial partial, type 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy - childhood onset v1.0 LIPE Ivone Leong commented on gene: LIPE: As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Lipodystrophy - childhood onset v1.0 ZMPSTE24 Ivone Leong commented on gene: ZMPSTE24
Lipodystrophy - childhood onset v1.0 PPARG Ivone Leong commented on gene: PPARG
Lipodystrophy - childhood onset v1.0 POLD1 Ivone Leong commented on gene: POLD1
Lipodystrophy - childhood onset v1.0 LMNA Ivone Leong commented on gene: LMNA
Lipodystrophy - childhood onset v1.0 CAVIN1 Ivone Leong commented on gene: CAVIN1
Lipodystrophy - childhood onset v1.0 CAVIN1 Ivone Leong Deleted their review
Lipodystrophy - childhood onset v1.0 CAVIN1 Ivone Leong Deleted their comment
Lipodystrophy - childhood onset v1.0 CAVIN1 Ivone Leong commented on gene: CAVIN1
Lipodystrophy - childhood onset v1.0 BSCL2 Ivone Leong commented on gene: BSCL2
Lipodystrophy - childhood onset v1.0 AGPAT2 Ivone Leong commented on gene: AGPAT2
Lipodystrophy - childhood onset v1.0 Ellen McDonagh promoted panel to version 1.0
Lipodystrophy - childhood onset v0.17 CIDEC Ivone Leong Marked gene: CIDEC as ready
Lipodystrophy - childhood onset v0.17 CIDEC Ivone Leong Gene: cidec has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v0.17 AKT2 Ivone Leong Marked gene: AKT2 as ready
Lipodystrophy - childhood onset v0.17 AKT2 Ivone Leong Gene: akt2 has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v0.17 ADRA2A Ivone Leong Marked gene: ADRA2A as ready
Lipodystrophy - childhood onset v0.17 ADRA2A Ivone Leong Gene: adra2a has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Marked gene: LIPE as ready
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Gene: lipe has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong commented on gene: LIPE: Keven Colclough (Royal Devon & Exeter Hospital) has agreed that LIPE should be promoted to green gene status.
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Marked gene: LIPE as ready
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Gene: lipe has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Deleted their comment
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Classified gene: LIPE as Green List (high evidence)
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Added comment: Comment on list classification: Promoted from red to green gene. LIPE was included in the gene list as a red gene as suggested by Kevin Colclough (Royal Devon & Exeter Hospital). LIPE is confirmed to be associated to partial familial lipodystrophy in OMIM but not in Gene2Phenotype. There are 3 unrelated cases of patients with partial lipodystrophy with different variants in the LIPE gene. Therefore, LIPE has been promoted from red to green status.
Lipodystrophy - childhood onset v0.17 LIPE Ivone Leong Gene: lipe has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.16 LIPE Ivone Leong Classified gene: LIPE as Green List (high evidence)
Lipodystrophy - childhood onset v0.16 LIPE Ivone Leong Added comment: Comment on list classification: Promoted from red to green gene. LIPE was included in the gene list as a red gene as suggested by Kevin Colclough (Royal Devon & Exeter Hospital). LIPE is confirmed to be associated to partial familial lipodystrophy in OMIM but not in Gene2Phenotype. There are 3 unrelated cases of patients with partial lipodystrophy with different variants in the LIPE gene. Therefore, LIPE has been promoted from red to green status.
Lipodystrophy - childhood onset v0.16 LIPE Ivone Leong Gene: lipe has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.15 LIPE Ivone Leong Publications for gene: LIPE were set to 27862896
Lipodystrophy - childhood onset v0.14 ADRA2A Ivone Leong Marked gene: ADRA2A as ready
Lipodystrophy - childhood onset v0.14 ADRA2A Ivone Leong Added comment: Comment when marking as ready: ARDRA2A was included in this panel as a red gene as suggested by Keven Colclough (Royal Devon & Exeter Hospital). Familial partial lipodystrophy is not confirmed to be associated with ADRA2A in OMIM or Gene2Phenotype. There is only one variant reported (PMID: 27376152).
Lipodystrophy - childhood onset v0.14 ADRA2A Ivone Leong Gene: adra2a has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v0.14 AKT2 Ivone Leong Marked gene: AKT2 as ready
Lipodystrophy - childhood onset v0.14 AKT2 Ivone Leong Added comment: Comment when marking as ready: AKT2 was included in the gene list as suggested by Kevin Colclough (Royal Devon & Exeter Hospital). AKT2 is a red gene in the Insulin resistance (including lipodystrophy) (Version 1.6) panel and only 1 variant has been reported when this gene was reviewed for that panel (2016). There has not been any new variants for this gene.
Lipodystrophy - childhood onset v0.14 AKT2 Ivone Leong Gene: akt2 has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v0.14 AKT2 Ivone Leong Publications for gene: AKT2 were set to
Lipodystrophy - childhood onset v0.13 AKT2 Ivone Leong Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900 to Diabetes mellitus, type II, 125853; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900; Partial lipodystrophy
Lipodystrophy - childhood onset v0.12 AKT2 Ivone Leong Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853 to Diabetes mellitus, type II, 125853; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900
Lipodystrophy - childhood onset v0.11 CIDEC Ivone Leong Marked gene: CIDEC as ready
Lipodystrophy - childhood onset v0.11 CIDEC Ivone Leong Added comment: Comment when marking as ready: CIDEC was included in the gene list as suggested by Kevin Colclough (Royal Devon & Exeter Hospital). CIDEC is a red gene in the Insulin resistance (including lipodystrophy) (Version 1.6) panel and only 1 variant has been reported when this gene was reviewed for that panel (2016). There has not been any new variants for this gene.
Lipodystrophy - childhood onset v0.11 CIDEC Ivone Leong Gene: cidec has been classified as Red List (Low Evidence).
Lipodystrophy - childhood onset v0.11 PLIN1 Ivone Leong Marked gene: PLIN1 as ready
Lipodystrophy - childhood onset v0.11 PLIN1 Ivone Leong Gene: plin1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v0.11 ZMPSTE24 Ivone Leong Marked gene: ZMPSTE24 as ready
Lipodystrophy - childhood onset v0.11 ZMPSTE24 Ivone Leong Gene: zmpste24 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 PPARG Ivone Leong Marked gene: PPARG as ready
Lipodystrophy - childhood onset v0.11 PPARG Ivone Leong Gene: pparg has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 POLD1 Ivone Leong Marked gene: POLD1 as ready
Lipodystrophy - childhood onset v0.11 POLD1 Ivone Leong Gene: pold1 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 LMNA Ivone Leong Marked gene: LMNA as ready
Lipodystrophy - childhood onset v0.11 LMNA Ivone Leong Gene: lmna has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 CAVIN1 Ivone Leong Marked gene: CAVIN1 as ready
Lipodystrophy - childhood onset v0.11 CAVIN1 Ivone Leong Gene: cavin1 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 BSCL2 Ivone Leong Marked gene: BSCL2 as ready
Lipodystrophy - childhood onset v0.11 BSCL2 Ivone Leong Gene: bscl2 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 AGPAT2 Ivone Leong Marked gene: AGPAT2 as ready
Lipodystrophy - childhood onset v0.11 AGPAT2 Ivone Leong Gene: agpat2 has been classified as Green List (High Evidence).
Lipodystrophy - childhood onset v0.11 LIPE Ivone Leong gene: LIPE was added
gene: LIPE was added to Lipodystrophy - childhood onset. Sources: Expert list,Expert Review
Mode of inheritance for gene: LIPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPE were set to 27862896
Phenotypes for gene: LIPE were set to Lipodystrophy, familial partial, type 6, 615980
Lipodystrophy - childhood onset v0.10 ADRA2A Ivone Leong gene: ADRA2A was added
gene: ADRA2A was added to Lipodystrophy - childhood onset. Sources: Expert list,Literature
Mode of inheritance for gene: ADRA2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADRA2A were set to 27376152
Phenotypes for gene: ADRA2A were set to No OMIM number; familial partial lipodystrophy
Lipodystrophy - childhood onset v0.9 AKT2 Ivone Leong gene: AKT2 was added
gene: AKT2 was added to Lipodystrophy - childhood onset. Sources: Expert list
Mode of inheritance for gene: AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: AKT2 were set to Diabetes mellitus, type II, 125853
Lipodystrophy - childhood onset v0.8 CIDEC Ivone Leong gene: CIDEC was added
gene: CIDEC was added to Lipodystrophy - childhood onset. Sources: Expert list
Mode of inheritance for gene: CIDEC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CIDEC were set to Lipodystrophy, familial partial, type 5, 615238
Lipodystrophy - childhood onset v0.7 PLIN1 Ellen McDonagh Classified gene: PLIN1 as Amber List (moderate evidence)
Lipodystrophy - childhood onset v0.7 PLIN1 Ellen McDonagh Added comment: Comment on list classification: This gene was downgraded from Green to Amber due to the findings of PMID: 30020498 - variants in this gene predicted to cause haplosufficiency are not a cause of familial partial lipodystrophy.
Lipodystrophy - childhood onset v0.7 PLIN1 Ellen McDonagh Gene: plin1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy - childhood onset v0.6 PLIN1 Ellen McDonagh Publications for gene: PLIN1 were set to 21345103; 25114292
Lipodystrophy - childhood onset v0.3 ZMPSTE24 Sarah Leigh gene: ZMPSTE24 was added
gene: ZMPSTE24 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: ZMPSTE24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZMPSTE24 were set to 18435794; 16297189; 20034068; 12913070; 15317753
Phenotypes for gene: ZMPSTE24 were set to Mandibuloacral dysplasia with type B lipodystrophy, 608612
Lipodystrophy - childhood onset v0.3 PPARG Sarah Leigh gene: PPARG was added
gene: PPARG was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: PPARG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPARG were set to Insulin resistance, severe, digenic 604367; Lipodystrophy, familial partial, type 3 604367
Lipodystrophy - childhood onset v0.3 POLD1 Sarah Leigh gene: POLD1 was added
gene: POLD1 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: POLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLD1 were set to 25131834; 26172944; 23770608
Phenotypes for gene: POLD1 were set to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, 615381
Lipodystrophy - childhood onset v0.3 PLIN1 Sarah Leigh gene: PLIN1 was added
gene: PLIN1 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: PLIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLIN1 were set to 21345103; 25114292
Phenotypes for gene: PLIN1 were set to Lipodystrophy, familial partial, type 4, 613877
Lipodystrophy - childhood onset v0.3 LMNA Sarah Leigh gene: LMNA was added
gene: LMNA was added to Lipodystrophy - childhood onset. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Eligibility statement prior genetic testing,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LMNA were set to Lipodystrophy, familial partial, 2, 151660
Lipodystrophy - childhood onset v0.3 BSCL2 Sarah Leigh gene: BSCL2 was added
gene: BSCL2 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: BSCL2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BSCL2 were set to Lipodystrophy, congenital generalized, type 2, 269700
Lipodystrophy - childhood onset v0.3 AGPAT2 Sarah Leigh gene: AGPAT2 was added
gene: AGPAT2 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: AGPAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AGPAT2 were set to Lipodystrophy, congenital generalized, type 1, 608594
Lipodystrophy - childhood onset v0.3 CAVIN1 Sarah Leigh gene: CAVIN1 was added
gene: CAVIN1 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: CAVIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAVIN1 were set to 19726876
Phenotypes for gene: CAVIN1 were set to Lipodystrophy, congenital generalized, type 4, 613327
Lipodystrophy - childhood onset v0.1 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual
Lipodystrophy - childhood onset v0.0 Ellen McDonagh Added Panel Lipodystrophy - childhood onset
Set panel types to: GMS Rare Disease