Early-Onset Movement Disorder Syndrome Caused by Biallelic Variants in PDE1B Encoding Phosphodiesterase 1B.

ABSTRACT:

Background

Breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in basal ganglia cells through hydrolysis of diesteric bonds, primarily by PDE10A and PDE1B, is essential for normal human movement. While biallelic loss-of-function variants in PDE10A are known to cause hyperkinetic movement disorders, the role of PDE1B in human disease has not been characterized.

Objectives

We aimed to define the phenotypic and molecular characteristics of a novel autosomal recessive disorder caused by biallelic PDE1B variants.

Methods

Clinical phenotyping by senior geneticists and neurologists, followed by whole exome sequencing, segregation analysis (Sanger sequencing), and molecular studies, including mini-gene splicing assays and protein studi

SUBMITTER: Poleg T 

PROVIDER: S-EPMC12485581 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature