Hereditary ataxia with onset in adulthood

Gene: PRPS1

I don't know

Comment on mode of inheritance: All female cases from the three families were reported with X-linked dominant variants in PRPS1 gene. Hence, the MOI should be changed to "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)".

Created: 7 Jul 2023, 8:27 p.m. | Last Modified: 7 Jul 2023, 8:27 p.m.

Panel Version: 4.15

Comment on list classification: As reviewed by Zornitza Stark, three families were reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.

Created: 7 Jul 2023, 8:23 p.m. | Last Modified: 7 Jul 2023, 8:24 p.m.

Panel Version: 4.13

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
cerebellar ataxia, MONDO:0000437

Publications

• 25491489
• 28967191
• 33898739

I don't know

PMID: 25491489:
Heterozygous missense variant, loss of function - PRS enzyme deficiency showed.
Proband and her mother have various degrees of ataxia (examinations at 34yrs and 70yrs, respectively), peripheral neuropathy and hearing loss beyond the ophthalmological symptoms, whereas the phenotype of the affected older sister (36yo) is currently confined to the eye and milder.

PMID: 28967191
in one of the families, heterozygous variants in proband with hearing loss and ataxia developed in the proband in her forties, and ocular manifestations of retinal changes and disc pallor were first confirmed in the two affected daughters in their twenties.

PMID: 33898739:
Heterozygous de novo missense variant in a 30yo female individual, presented with a 5-year history of progressive ataxia. She also had congenital strabismus, infantile-onset hearing loss, and a retinal dystrophy with progressive visual loss for the past 10 years.
Sources: Literature

Created: 11 Oct 2021, 9:35 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Ataxia; deafness; eye disease

Publications

• 33898739
• 28967191
• 25491489