Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns.
Mutations in the GJB2 (connexin 26, Cx26) gene are the major cause of nonsyndromic hearing impairment in many populations. Genetic testing offers opportunities to determine the cause of deafness and predict the course of hearing, enabling the prognostication of language development. In the current study, we compared severity of hearing impairment in 60 patients associated with biallelic GJB2 mutations and assessed the correlation of genotypes and phenotypes. Within a spectrum of GJB2 mutations found in the Japanese population, the phenotype of the most prevalent mutation, 235delC, was found to show more severe hearing impairment than that of V37I, which is the second most frequent mutation. The results of the present study, taken together with phenotypes caused by other types of mutations, support the general rule that phenotypes caused by the truncating GJB2 mutations are more severe than those caused by missense mutations. The present in vitro study further confirmed that differences in phenotypes could be explained by the protein expression pattern.
Oguchi
Tomohiro
T
Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Ohtsuka
Akihiro
A
Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Hashimoto
Shigenari
S
Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Oshima
Aki
A
Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Abe
Satoko
S
Abe ENT Clinic, 2-2-5 Nishi-magome, Ota-ku, Tokyo, 143-0026, Japan.
Kobayashi
Yumiko
Y
Department of Otorhinolaryngology, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
Nagai
Kyoko
K
Department of Otorhinolaryngology, Gunma University School of Medicine, 4-2 Aramaki-machi, Maebashi, Gunma, 371-8510, Japan.
Matsunaga
Tatsuo
T
Department of Otolaryngology/Laboratory of Auditory Disorders, National Tokyo Medical Center, National Institute of Sensory Organs, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan.
Iwasaki
Satoshi
S
Department of Otorhinolaryngology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.
Nakagawa
Takashi
T
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Usami
Shin-Ichi
SI
Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. usami@hsp.md.shinshu-u.ac.jp.
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26