title: Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.
abstract: 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.
authors.affiliation: Department of Otolaryngology, University of Miami, FL 33136, USA.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ouyang
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Jin
authors.forename: Youqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.forename: Albena
authors.initials: A
authors.lastname: Kantardzhieva
authors.forename: Roland D
authors.initials: RD
authors.lastname: Eavey
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Li L
authors.initials: LL
authors.lastname: Du
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Chen
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Maikun
authors.initials: M
authors.lastname: Teng
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D041321:Chromosomes, Human, X; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012268:Ribose-Phosphate Pyrophosphokinase / Q000235:genetics*
chemical_list: C510474:PRPS1 protein, human; D012268:Ribose-Phosphate Pyrophosphokinase