Skeletal dysplasia
Gene: PDE3A
Brachydactylies (with extraskeletal manifestations) gp of SD - >3 cases. missense variants clustered in exon 4; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Hypertension and brachydactyly syndrome, 112410
Publications
Mode of pathogenicity
Other - please provide details in the comments
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PDE3A; Initial rating suggestion: greenCreated: 6 Mar 2019, 11:36 a.m.
Mutations appear to be gain of function missense as per PMID 25961942*. 6 missense variants identified in unrelated families with dominant hypertension with brachydactyly (HTNB)
*Article link https://www.nature.com/articles/ng.3302
The article PMID: 9696728 gives more information about the clinical phenotype - their Canadian and American families showed linkage to an area of chromosome 12p containing PDE3A, as had a previous Turkish family.
http://annals.org/aim/fullarticle/711593/families-autosomal-dominant-brachydactyly-type-e-short-stature-severe-hypertension.
Sources: LiteratureCreated: 10 Sep 2018, 3:22 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Hypertension and brachydactyly syndrome 112410
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Hypertension and brachydactyly syndrome, 112410 for gene: PDE3A
Source NHS GMS was added to PDE3A. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for gene: PDE3A were changed from Hypertension and brachydactyly syndrome 112410 to Hypertension and brachydactyly syndrome, 112410
Publications for gene: PDE3A were set to PMID: 25961942; 9696728
Gene: pde3a has been classified as Green List (High Evidence).
gene: PDE3A was added gene: PDE3A was added to Unexplained skeletal dysplasia. Sources: Literature Mode of inheritance for gene: PDE3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PDE3A were set to PMID: 25961942; 9696728 Phenotypes for gene: PDE3A were set to Hypertension and brachydactyly syndrome 112410 Penetrance for gene: PDE3A were set to Complete Mode of pathogenicity for gene: PDE3A was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PDE3A was set to GREEN