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Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIK3R1.
Tag Q3_23_NHS_review was removed from gene: PIK3R1.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram commented on gene: PIK3R1: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.51 PIK3R1 Achchuthan Shanmugasundram Source Expert Review Green was added to PIK3R1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
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 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 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