Childhood onset dystonia, chorea or related movement disorder

Gene: NUP54

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 9:18 a.m. | Last Modified: 11 Oct 2023, 9:18 a.m.

Panel Version: 3.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence (3 unrelated cases) for rating this gene as GREEN in the next GMS review.

Created: 1 Jun 2023, 8:13 p.m. | Last Modified: 1 Jun 2023, 8:13 p.m.

Panel Version: 3.11

PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Western blots showed reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature

Created: 1 Jun 2023, 8:12 p.m. | Last Modified: 1 Jun 2023, 8:15 p.m.

Panel Version: 3.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Early-onset dystonia

Publications

• 36333996