Identification of Two Novel Compound Heterozygous PTPRQ Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family

Xue Gao; Yu Su; Yu-Lan Chen; Ming-Yu Han; Yong-Yi Yuan; Jin-Cao Xu; Feng Xin; Mei-Guang Zhang; Sha-Sha Huang; Guo-Jian Wang; Dong-Yang Kang; Li-Ping Guan; Jian-Guo Zhang; Pu Dai

doi:10.1371/journal.pone.0124757

Identification of Two Novel Compound Heterozygous PTPRQ Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family

PLoS One. 2015 Apr 28;10(4):e0124757. doi: 10.1371/journal.pone.0124757. eCollection 2015.

Authors

Xue Gao¹, Yu Su², Yu-Lan Chen³, Ming-Yu Han⁴, Yong-Yi Yuan², Jin-Cao Xu⁵, Feng Xin⁴, Mei-Guang Zhang⁵, Sha-Sha Huang⁴, Guo-Jian Wang⁴, Dong-Yang Kang⁴, Li-Ping Guan³, Jian-Guo Zhang³, Pu Dai²

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China; Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, P. R. China; Department of Otorhinolaryngology, the Second Artillery General Hospital, Beijing, P. R. China.
² Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China; Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, P. R. China.
³ BGI-Shenzhen, Shenzhen, 518083, China.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
⁵ Department of Otorhinolaryngology, the Second Artillery General Hospital, Beijing, P. R. China.

Abstract

Mutations in PTPRQ are associated with deafness in humans due to defects of stereocilia in hair cells. Using whole exome sequencing, we identified responsible gene of family 1572 with autosomal recessively non-syndromic hearing loss (ARNSHL). We also used DNA from 74 familial patients with ARNSHL and 656 ethnically matched control chromosomes to perform extended variant analysis. We identified two novel compound heterozygous missense mutations, c. 3125 A>G p.D1042G (maternal allele) and c.5981 A>G p.E1994G (paternal allele), in the PTPRQ gene, as the cause of recessively inherited sensorineural hearing loss in family 1572. Both variants co-segregated with hearing loss phenotype in family 1572, but were absent in 74 familial patients. Heterozygosity for c. 3125 A>G was identified in two samples from unaffected Chinese individuals (656 chromosomes). Therefore, the hearing loss in this family was caused by two novel compound heterozygous mutations in PTPRQ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Asian People / genetics*
Base Sequence
Child
DNA Mutational Analysis
Exome / genetics
Family
Female
Genes, Recessive*
Genetic Association Studies*
Genetic Predisposition to Disease*
Hearing Loss / genetics*
Heterozygote
Humans
Male
Models, Molecular
Molecular Sequence Data
Mutant Proteins / chemistry
Mutation / genetics*
Pedigree
Receptor-Like Protein Tyrosine Phosphatases, Class 3 / chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics*
Young Adult

Substances

Mutant Proteins
Receptor-Like Protein Tyrosine Phosphatases, Class 3

Grants and funding

This work was supported by grants from the Project of the National Natural Science Foundation of China (30801285, 81230020, 81200751, 81371098, 81371096, 81400471, 81371352), grants from China Postdoctoral Science Foundation (2012M521878, 2013T60947), a grant from the Project of Beijing Natural Science Foundation (7132177, 7122172), a grant from Minister of Science and Technology of China (2012BAI09B02), a grant from Military Twelfth Five-year Project of China (CWS115034), grants from the National Basic Research Program of China (973 Program) (2014CB541706, 2014CB541701) and a grant from Minister of Health of China (201202005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.