Syndromic Retinopathy

Gene: PRPS1

Green List (high evidence)

Phosphoribosylpyrophosphate synthetase catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for the de novo and salvage pathways of purine and pyrimidine biosynthesis.

Both increased and decreased enzyme activity has been linked to disease.
Sources: Expert Review

Created: 7 Feb 2021, 2:56 a.m.

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

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

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