The responsible genes in Japanese deafness patients and clinical application using Invader assay.
Discovery of deafness genes has progressed but clinical application lags because of the genetic heterogeneity. To establish clinical application strategy, we reviewed the frequency and spectrum of mutations found in Japanese hearing loss patients and compared them to those in populations of European ancestry. Screening revealed that in Japanese, mutations in GJB2, SLC26A4, and CDH23, and the mitochondrial 12S rRNA are the major causes of hearing loss. Also, mutations in KCNQ4, TECTA, COCH, WFS1, CRYM, COL9A3, and KIAA1199 were found in independent autosomal dominant families. Interestingly, spectrums of GJB2, SLC26A4, and CDH23 mutations in Japanese were quite different from those in Europeans. Simultaneous screening of multiple deafness mutations based on the mutation spectrum of a corresponding population using an Invader panel revealed that approximately 30% of subjects could be diagnosed. This assay will enable us to detect deafness mutations in an efficient and practical manner in the clinical platform. We conclude that specific racial populations may have unique deafness gene epidemiologies; therefore, ethnic background should be considered when genetic testing is performed. Simultaneous examination of multiple mutations based on a population's spectrum may be appropriate and effective for detecting deafness genes, facilitating precise clinical diagnosis, appropriate counseling, and proper management.
Usami
Shin-Ichi
S
Department of Otorhinolaryngology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan. usami@hsp.md.shinshu-u.ac.jp
Wagatsuma
Michio
M
Fukuoka
Hisakuni
H
Suzuki
Hiroaki
H
Tsukada
Keita
K
Nishio
Shinya
S
Takumi
Yutaka
Y
Abe
Satoko
S
D001692:Biological Transport; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D003638:Deafness / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D015995:Prevalence; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D000076988:Sulfate Transporters; D000090803:mu-Crystallins
C442480:CDH23 protein, human; C000716469:CRYM protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; D000090803:mu-Crystallins