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Novel PRPS1 gain-of-function mutation in a patient with congenital hyperuricemia and facial anomalies
Tech Univ Dresden, Inst Klin Genet, Dresden, Germany..
Tech Univ Dresden, Inst Klin Genet, Dresden, Germany..
Tech Univ Dresden, Inst Klin Genet, Dresden, Germany..
Tech Univ Dresden, Inst Klin Genet, Dresden, Germany..
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2017 (English)In: American Journal of Medical Genetics. Part A, ISSN 1552-4825, E-ISSN 1552-4833, Vol. 173, no 10, p. 2736-2742Article in journal (Refereed) Published
Abstract [en]

Phosphoribosylpyrophosphate synthetase (PRPPS) superactivity (OMIM 300661) is a rare inborn error of purine metabolism that is caused by gain-of-function mutations in the X-chromosomal gene PRPS1 (Xq22.3). Clinical characteristics include congenital hyperuricemia and hyperuricosuria, gouty arthritis, urolithiasis, developmental delay, hypotonia, recurrent infections, short stature, and hearing loss. Only eight families with PRPPS superactivity and PRPS1 gain-of-function mutations have been reported to date. We report on a 7-year-old boy with congenital hyperuricemia, urolithiasis, developmental delay, short stature, hypospadias, and facial dysmorphisms. His mother also suffered from hyperuricemia that was diagnosed at age 13 years. A novel PRPS1 missense mutation (c.573G>C, p.[Leu191Phe]) was detected in the proband and his mother. Enzyme activity analysis confirmed superactivity of PRPP synthetase. Analysis of the crystal structure of human PRPPS suggests that the Leu191Phe mutation affects the architecture of both allosteric sites, thereby preventing the allosteric inhibition of the enzyme. The family reported here broadens the clinical spectrum of PRPPS superactivity and indicates that this rare metabolic disorder might be associated with a recognizable facial gestalt.

Place, publisher, year, edition, pages
WILEY , 2017. Vol. 173, no 10, p. 2736-2742
Keywords [en]
hyperuricemia, phosphoribosylpyrophosphate synthetase superactivity, PRPS1
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-336298DOI: 10.1002/ajmg.a.38359ISI: 000411036600023PubMedID: 28742244OAI: oai:DiVA.org:uu-336298DiVA, id: diva2:1176843
Available from: 2018-01-23 Created: 2018-01-23 Last updated: 2018-01-23Bibliographically approved

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Dobritzsch, Doreen

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