A homozygous loss-of-function mutation in PDE2A associated to early-onset hereditary chorea.

ABSTRACT:

Background

We investigated a family that presented with an infantile-onset chorea-predominant movement disorder, negative for NKX2-1, ADCY5, and PDE10A mutations.

Methods

Phenotypic characterization and trio whole-exome sequencing was carried out in the family.

Results

We identified a homozygous mutation affecting the GAF-B domain of the 3',5'-cyclic nucleotide phosphodiesterase PDE2A gene (c.1439A>G; p.Asp480Gly) as the candidate novel genetic cause of chorea in the proband. PDE2A hydrolyzes cyclic adenosine/guanosine monophosphate and is highly expressed in striatal medium spiny neurons. We functionally characterized the p.Asp480Gly mutation and found that it severely decreases the enzymatic activity of PDE2A. In addition, we showed equivalent expression in human an

SUBMITTER: Salpietro V 

PROVIDER: S-EPMC5873427 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature