Hereditary ataxia

Gene: NUS1

Green List (high evidence)

Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available (~10 unrelated patients and functional evidence) for the promotion of this gene to green rating.

Created: 12 Nov 2024, 10:01 p.m. | Last Modified: 12 Nov 2024, 10:01 p.m.

Panel Version: 1.337

PMID:31656175 reported two unrelated patients with a novel de novo NUS1 variant and they presented with epileptic seizures with involuntary movement, ataxia, intellectual disability and scoliosis.

PMID:32485575 reported the identification of a novel heterozygous frameshift variant in NUS1 gene in five patients from a family with epilepsy. They all had cerebellar ataxia and tremor.

PMID:32959737 reported a 34-year-old female with NUS1 variant with a prominent and progressive generalised dystonia. She developed a slight head tremor at 18 months of age. Intellectual disability was diagnosed by second grade. She developed a mild but progressive gait ataxia, dysarthria, and dyscoordination of the hands.

PMID:33731878 reported three patients with de novo heterozygous NUS1 variants, of which two patients presented with ataxia. The third patient had no ataxia but was noted to have dysarthria. There is also functional evidence available from patient fibroblasts and zebrafish models.

PMID:38291835 reported five unrelated patients with NUS1 variants. They had onset of movement disorders ranging from birth to 13 years of age and four of them had mild gait ataxia.

Created: 12 Nov 2024, 9:58 p.m. | Last Modified: 12 Nov 2024, 9:58 p.m.

Panel Version: 1.334

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hereditary ataxia, MONDO:0100309

Publications

• 31656175
• 32485575
• 32959737
• 33731878
• 38291835

Green List (high evidence)

Multiple patients (see below) with de novo or heterozygous variants reported. The phenotype include ID, seizures and/or movement disorder (including tremor, ataxia, dystonia). Functional analysis of patients fibroblasts shows"de novo NUS1 variants reduce NgBR and Niemann–Pick type C2 (NPC2) protein amount, impair dolichol biosynthesis, and cause lysosomal cholesterol accumulation." (Yu et al,m 2021). Movement abnormalities and similar metabolic dysfunction in zebrafish model.

3 patients with ataxia reported in: PMID: 33731878
One patient with dystonia reported in: PMID: 32334381
One family with ataxia reported in: PMID: 32485575
Two cases with ataxia reported in: PMID: 31656175

Additionally, two cases from one family with homozygous missense variant, but NO ataxia is reported:PMID: 25066056
Sources: Literature

Created: 27 Jun 2021, 2:49 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
intellectual disability; seizures; ataxia; dystonia; tremor

Publications

• 33731878
• 32334381
• 32485575
• 31656175