Lipodystrophy - childhood onset
Gene: MFN2
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.Created: 7 Aug 2023, 12:59 p.m. | Last Modified: 7 Aug 2023, 12:59 p.m.
Panel Version: 4.31
Comment on phenotypes: Autosomal recessive variants in this gene have been associated with cephalothoracic lipodystrophy in OMIM (MIM #151800), but not in Gene2Phenotype.Created: 7 Aug 2023, 12:56 p.m. | Last Modified: 7 Aug 2023, 12:56 p.m.
Panel Version: 4.29
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.Created: 2 Aug 2023, 11:35 a.m. | Last Modified: 7 Aug 2023, 12:14 p.m.
Panel Version: 4.27
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
MFN2-associated multiple lipomatosis, lipodystrophy, severe insulin resistance, axonal sensorimotor neuropathy
Publications
Mode of pathogenicity
Other
Tag Q3_23_promote_green tag was added to gene: MFN2. Tag Q3_23_NHS_review tag was added to gene: MFN2.
Gene: mfn2 has been classified as Amber List (Moderate Evidence).
Publications for gene: MFN2 were set to 26085578; 28414270; 3015806
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
Publications for gene: MFN2 were set to
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