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

Xue Z 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 journalArticle

61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)65-71
Number of pages7
JournalAmerican Journal of Human Genetics
Volume86
Issue number1
DOIs
StatePublished - Jan 6 2010

Fingerprint

Deafness
Mutation
Ribose-Phosphate Pyrophosphokinase
Vestibular Hair Cells
Genes
Spiral Ganglion
Cochlea
Enzyme Assays
Genetic Testing
Missense Mutation
Fibroblasts
Erythrocytes
Nonsyndromic Deafness

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2. / Liu, Xue Z; Han, Dongyi; Li, Jianzhong; Han, Bing; Ouyang, Xiaomei; Cheng, Jing; Li, Xu; Jin, Zhanguo; Wang, Youqin; Bitner-Glindzicz, Maria; Kong, Xiangyin; Xu, Heng; Kantardzhieva, Albena; Eavey, Roland D.; Seidman, Christine E.; Seidman, Jonathan G.; Du, Li L.; Chen, Zheng Yi; Dai, Pu; Teng, Maikun; Yan, Denise; Yuan, Huijun.

In: American Journal of Human Genetics, Vol. 86, No. 1, 06.01.2010, p. 65-71.

Research output: Contribution to journalArticle

Liu, XZ, Han, D, Li, J, Han, B, Ouyang, X, Cheng, J, Li, X, Jin, Z, Wang, Y, Bitner-Glindzicz, M, Kong, X, Xu, H, Kantardzhieva, A, Eavey, RD, Seidman, CE, Seidman, JG, Du, LL, Chen, ZY, Dai, P, Teng, M, Yan, D & Yuan, H 2010, 'Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2', American Journal of Human Genetics, vol. 86, no. 1, pp. 65-71. https://doi.org/10.1016/j.ajhg.2009.11.015
Liu, Xue Z ; Han, Dongyi ; Li, Jianzhong ; Han, Bing ; Ouyang, Xiaomei ; Cheng, Jing ; Li, Xu ; Jin, Zhanguo ; Wang, Youqin ; Bitner-Glindzicz, Maria ; Kong, Xiangyin ; Xu, Heng ; Kantardzhieva, Albena ; Eavey, Roland D. ; Seidman, Christine E. ; Seidman, Jonathan G. ; Du, Li L. ; Chen, Zheng Yi ; Dai, Pu ; Teng, Maikun ; Yan, Denise ; Yuan, Huijun. / Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2. In: American Journal of Human Genetics. 2010 ; Vol. 86, No. 1. pp. 65-71.
@article{e9752dab7e0e43c0a948c4bfd66c75c9,
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.",
author = "Liu, {Xue Z} and Dongyi Han and Jianzhong Li and Bing Han and Xiaomei Ouyang and Jing Cheng and Xu Li and Zhanguo Jin and Youqin Wang and Maria Bitner-Glindzicz and Xiangyin Kong and Heng Xu and Albena Kantardzhieva and Eavey, {Roland D.} and Seidman, {Christine E.} and Seidman, {Jonathan G.} and Du, {Li L.} and Chen, {Zheng Yi} and Pu Dai and Maikun Teng and Denise Yan and Huijun Yuan",
year = "2010",
month = "1",
day = "6",
doi = "10.1016/j.ajhg.2009.11.015",
language = "English",
volume = "86",
pages = "65--71",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2

AU - Liu, Xue Z

AU - Han, Dongyi

AU - Li, Jianzhong

AU - Han, Bing

AU - Ouyang, Xiaomei

AU - Cheng, Jing

AU - Li, Xu

AU - Jin, Zhanguo

AU - Wang, Youqin

AU - Bitner-Glindzicz, Maria

AU - Kong, Xiangyin

AU - Xu, Heng

AU - Kantardzhieva, Albena

AU - Eavey, Roland D.

AU - Seidman, Christine E.

AU - Seidman, Jonathan G.

AU - Du, Li L.

AU - Chen, Zheng Yi

AU - Dai, Pu

AU - Teng, Maikun

AU - Yan, Denise

AU - Yuan, Huijun

PY - 2010/1/6

Y1 - 2010/1/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=73149115319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73149115319&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2009.11.015

DO - 10.1016/j.ajhg.2009.11.015

M3 - Article

C2 - 20021999

AN - SCOPUS:73149115319

VL - 86

SP - 65

EP - 71

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -