A novel pore-region mutation, c.887G > A (p.G296D) in KCNQ4, causing hearing loss in a Chinese family with autosomal dominant non-syndromic deafness 2.
Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. The KCNQ4 channel belongs to a family of potassium ion channels that play crucial roles in physiology and disease. Mutations in KCNQ4 underlie deafness non-syndromic autosomal dominant 2, a subtype of autosomal dominant, progressive, high-frequency hearing loss.



A six-generation Chinese family from Hebei Province with autosomal dominantly inherited, sensorineural, postlingual, progressive hearing loss was enrolled in this study. Mutation screening of 129 genes associated with hearing loss was performed in five family members by next-generation sequencing (NGS). We also carried out variant analysis on DNA from 531 Chinese individuals with normal hearing as controls.



This family exhibits postlingual, progressive, symmetrical, bilateral, non-syndromic sensorineural hearing loss. NGS, bioinformatic analysis, and Sanger sequencing confirmed the co-segregation of a novel mutation [c.887G > A (p.G296D)] in KCNQ4 with the disease phenotype in this family. This mutation leads to a glycine-to-aspartic acid substitution at position 296 in the pore region of the KCNQ4 channel. This mutation affects a highly conserved glutamic acid. NGS is a highly efficient tool for identifying gene mutations causing heritable disease.



Progressive hearing loss is common in individuals with KCNQ4 mutations. NGS together with Sanger sequencing confirmed that the five affected members of this Chinese family inherited a missense mutation, c.887G > A (p.G296D), in exon 6 of KCNQ4. Our results increase the number of identified KCNQ4 mutations.
Department of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.|Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, 572013, China.
Bangqing
B
Huang
Department of Otorhinolaryngology, General Hospital of the Rocket Force, Beijing, 100088, China.
Yanping
Y
Liu
Department of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.|Department of Otorhinolaryngology, General Hospital of the Rocket Force, Beijing, 100088, China.
Xue
X
Gao
Department of Otorhinolaryngology, General Hospital of the Rocket Force, Beijing, 100088, China.
Jincao
J
Xu
Department of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. daipu301@vip.sina.com.
Pu
P
Dai
Department of Otolaryngology, The Second Hospital Of Hebei Medical University, Shijiazhuang, 050018, China. zqw301@163.com.
Qingwen
Q
Zhu
Department of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. yyymzh@163.com.
Yongyi
Y
Yuan
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001309:Auditory Threshold; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D055815:Young Adult
D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human; D004247:DNA
Autosomal dominant non-syndromic deafness 2; KCNQ4; Next-generation sequencing; Novel mutation