Lipodystrophy - childhood onset

Gene: PCYT1A

Green List (high evidence)

PCYT1A (phosphate cytidylyltransferase 1, choline, alpha)
EnsemblGeneIds (GRCh38): ENSG00000161217
EnsemblGeneIds (GRCh37): ENSG00000161217
OMIM: 123695, Gene2Phenotype
PCYT1A is in 9 panels

1 review

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 3 May 2024, 7:50 p.m. | Last Modified: 3 May 2024, 7:56 p.m.
Panel Version: 4.52
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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • Expert list
Phenotypes
  • Spondylometaphyseal dysplasia with cone-rod dystrophy, OMIM:608940
  • congenital generalized lipodystrophy, MONDO:0006536
  • Insulin resistance, HP:0000855
OMIM
123695
Clinvar variants
Variants in PCYT1A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 May 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: PCYT1A. Tag Q3_23_NHS_review was removed from gene: PCYT1A.

3 May 2024, Gel status: 3

Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to PCYT1A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

7 Aug 2023, Gel status: 2

Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green tag was added to gene: PCYT1A. Tag Q3_23_NHS_review tag was added to gene: PCYT1A.

7 Aug 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: pcyt1a has been classified as Amber List (Moderate Evidence).

7 Aug 2023, Gel status: 1

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

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

7 Aug 2023, Gel status: 1

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: PCYT1A were set to

2 Aug 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

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