Ataxia and cerebellar anomalies - narrow panel

Gene: PDE1B

Green List (high evidence)

Comment on list classification: Ataxia has been reported in four unrelated families and hence this gene can be promoted to green rating in the next GMS update.

Created: 18 Jul 2025, 9:13 p.m. | Last Modified: 18 Jul 2025, 9:13 p.m.

Panel Version: 8.12

As reviewed by Sarah Dixon, PMID:40492975 reported seven individuals from five unrelated families identified with biallelic PDE1B variants. Three truncating (p.Gln45Ter, p.Gln86Ter, p.Ser298Alafs*6) and three splicing variants (c.594 + 2 T>G, c.735 + 5G>A, c.837-1G>C) were identified from these patients in total.

They presented with an early-onset movement disorder characterised by hypotonia in infancy, progressing to ataxia and dystonia in early childhood, with motor and speech delay, and intellectual disability. Ataxia has been reported in five patients from four families, of which ataxia is of mild nature in one. Functional evidence is also available for these variants.

This gene has not yet been associated with relevant phenotypes in OMIM, Gene2Phenotype or ClinGen.

Created: 18 Jul 2025, 9:09 p.m. | Last Modified: 18 Jul 2025, 9:09 p.m.

Panel Version: 8.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
movement disorder, MONDO:0005395

Publications

• 40492975

Green List (high evidence)

PMID: 40492975
Biallelic LOF variants in PDE1B identified in seven individuals from five different families
Disorder characterized by hypotonia in infancy, progressing to ataxia and dystonia in early childhood, with developmental delay and intellectual disability
Sources: Literature

Created: 17 Jun 2025, 10:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hypotonia; ataxia; dystonia; developmental delay; intellectual disability

Publications

• PMID: 40492975