Identification of Two Novel Compound Heterozygous PTPRQ Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family.
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.
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.
Xue
X
Gao
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.
Yu
Y
Su
BGI-Shenzhen, Shenzhen, 518083, China.
Yu-Lan
YL
Chen
Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
Ming-Yu
MY
Han
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.
Yong-Yi
YY
Yuan
Department of Otorhinolaryngology, the Second Artillery General Hospital, Beijing, P. R. China.
Jin-Cao
JC
Xu
Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
Feng
F
Xin
Department of Otorhinolaryngology, the Second Artillery General Hospital, Beijing, P. R. China.
Mei-Guang
MG
Zhang
Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
Sha-Sha
SS
Huang
Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
Guo-Jian
GJ
Wang
Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
Dong-Yang
DY
Kang
BGI-Shenzhen, Shenzhen, 518083, China.
Li-Ping
LP
Guan
BGI-Shenzhen, Shenzhen, 518083, China.
Jian-Guo
JG
Zhang
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.
Pu
P
Dai
D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005190:Family; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
D050505:Mutant Proteins; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3