title: Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Oguchi
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohtsuka
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Shigenari
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Oshima
authors.affiliation: Abe ENT Clinic, 2-2-5 Nishi-magome, Ota-ku, Tokyo, 143-0026, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Otorhinolaryngology, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Otorhinolaryngology, Gunma University School of Medicine, 4-2 Aramaki-machi, Maebashi, Gunma, 371-8510, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nagai
authors.affiliation: 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.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of Otorhinolaryngology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwasaki
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. usami@hsp.md.shinshu-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Usami
mesh_terms: 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
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26