Lipodystrophy - childhood onset
Gene: PCYT1A
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.Created: 7 Aug 2023, 10:37 a.m. | Last Modified: 7 Aug 2023, 10:37 a.m.
Panel Version: 4.21
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).Created: 7 Aug 2023, 10:26 a.m. | Last Modified: 7 Aug 2023, 10:26 a.m.
Panel Version: 4.18
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.Created: 2 Aug 2023, 11:35 a.m. | Last Modified: 7 Aug 2023, 10:41 a.m.
Panel Version: 4.21
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spondylometaphyseal dysplasia with cone-rod dystrophy, Congenital lipodystrophy
Publications
Tag Q3_23_promote_green tag was added to gene: PCYT1A. Tag Q3_23_NHS_review tag was added to gene: PCYT1A.
Gene: pcyt1a has been classified as Amber List (Moderate Evidence).
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
Publications for gene: PCYT1A were set to
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