Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.
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.
Liu
Xuezhong
X
Department of Otolaryngology, University of Miami, FL 33136, USA.
Han
Dongyi
D
Li
Jianzhong
J
Han
Bing
B
Ouyang
Xiaomei
X
Cheng
Jing
J
Li
Xu
X
Jin
Zhanguo
Z
Wang
Youqin
Y
Bitner-Glindzicz
Maria
M
Kong
Xiangyin
X
Xu
Heng
H
Kantardzhieva
Albena
A
Eavey
Roland D
RD
Seidman
Christine E
CE
Seidman
Jonathan G
JG
Du
Li L
LL
Chen
Zheng-Yi
ZY
Dai
Pu
P
Teng
Maikun
M
Yan
Denise
D
Yuan
Huijun
H
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*
C510474:PRPS1 protein, human; D012268:Ribose-Phosphate Pyrophosphokinase