Ataxia - adult onset

Gene: PRPS1

I don't know

Likely falls within the spectrum of LoF-associated disease.

Created: 4 Oct 2021, 4:58 a.m. | Last Modified: 4 Oct 2021, 4:58 a.m.

Panel Version: 0.141

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
Ataxia; deafness; eye disease

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.

Created: 4 Oct 2021, 5:18 a.m. | Last Modified: 4 Oct 2021, 5:18 a.m.

Panel Version: 0.143

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.

Created: 4 Oct 2021, 4:52 a.m. | Last Modified: 4 Oct 2021, 4:52 a.m.

Panel Version: 0.141

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: 4 Oct 2021, 4:49 a.m.

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
Adult-onset progressive ataxia, congenital strabismus, infantile-onset hearing loss, retinal dystrophy

Publications

• 33898739
• 28967191
• 25491489

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

LOF missense - Arts syndrome, CMT, deafness
GOF missense - PRPS superactivity, Gout
- Females can be affected, with X skewing reported but not consistent. Females had epilepsy, hearing loss, optic atrophy, retinal dystrophy and/or neurological signs.
- some correlation btw residual activity and severity
- Two families with Arts syndrome, carrier females were mildly affected or asymptomatic.

No PTCs reported in ClinVar, but LOF is a known mechanism for missense and there are minimal PTCs in gnomAD – potentially lethal.

Variable expressivity: Yes

Created: 4 Dec 2020, 1:11 a.m. | Last Modified: 4 Dec 2020, 1:11 a.m.

Panel Version: 0.5527

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
Arts syndrome MIM#301835; Charcot-Marie-Tooth disease, X-linked recessive, 5 MIM#311070; Deafness, X-linked 1 MIM#304500; Gout, PRPS-related MIM#300661; Phosphoribosylpyrophosphate synthetase superactivity MIM#300661

Publications

• PMID: 32781272
• 17701896
• 7593598

Mode of pathogenicity
Other