Whole-exome sequencing identifies a de novo PDE3A variant causing autosomal dominant hypertension with brachydactyly type E syndrome: a case report.

ABSTRACT: BACKGROUND:Autosomal dominant hypertension with brachydactyly type E syndrome caused by pathogenic variants in the PDE3A gene was first reported in 2015. To date, there are only a few reports of this kind of syndrome. Other patients still lack a genetic diagnosis. CASE PRESENTATION:Whole-exome sequencing was performed in an 18-year-old female proband with a clinical diagnosis of hypertension with brachydactyly syndrome. Quantitative real-time PCR was used to identify pathogenic copy number variations (CNVs). After bioinformatics analysis and healthy control database filtering, we revealed a heterozygous missense PDE3A variant (c.1346G?>?A, p.Gly449Asp). The variant was absent in the ExAC database and located in a highly evolutionarily conserved cluster of reported PDE3A pathogenic variants. Importantly, this variant was predicted to affect protein function by both SIFT (score?=?0) and PolyPhen-2 (score?=?1). After Sanger sequencing, the variant was determined to be absent in the healthy parents of the proband as well as 800 ethnically and geographically matched healthy controls. CONCLUSION:We present a report linking a de novo PDE3A variant to autosomal dominant hypertension with brachydactyly type E syndrome.

SUBMITTER: Li X 

PROVIDER: S-EPMC7336660 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature