Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2

Xuezhong Liu, Dongyi Han, Jianzhong Li, Bing Han, Xiaomei Ouyang, Jing Cheng, Xu Li, Zhanguo Jin, Youqin Wang, Maria Bitner-Glindzicz, Xiangyin Kong, Heng Xu, Albena Kantardzhieva, Roland D. Eavey, Christine E. Seidman, Jonathan G. Seidman, Li L. Du, Zheng Yi Chen, Pu Dai, Maikun TengDenise Yan, Huijun Yuan

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


We report a large Chinese family with X-linked postlingual nonsyndromic hearing impairment in which the critical linkage interval spans a genetic distance of 5.41 cM and a physical distance of 15.1 Mb that overlaps the DFN2 locus. Mutation screening of the PRPS1 gene in this family and in the three previously reported DFN2 families identified four different missense mutations in PRPS1. These mutations result in a loss of phosphoribosyl pyrophosphate (PRPP) synthetase 1 activity, as was shown in silico by structural analysis and was shown in vitro by enzymatic activity assays in erythrocytes and fibroblasts from patients. By in situ hybridization, we demonstrate expression of Prps1 in murine vestibular and cochlea hair cells, with continuous expression in hair cells and postnatal expression in the spiral ganglion. Being the second identified gene associated with X-linked nonsyndromic deafness, PRPS1 will be a good candidate gene for genetic testing for X-linked nonsyndromic hearing loss.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalAmerican journal of human genetics
Issue number1
StatePublished - 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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