TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion.
TECTA gene encodes α-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype-phenotype correlations are associated with mutations of TECTA in exons according to α-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype-phenotype correlation, as well as the intracellular localization of missense mutations in the α-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype-phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of α-tectorin into the tectorial membrane.
Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
Hideaki
H
Moteki
Shin-ya
SY
Nishio
Shigenari
S
Hashimoto
Yutaka
Y
Takumi
Satoshi
S
Iwasaki
Norihito
N
Takeichi
Satoshi
S
Fukuda
Shin-ichi
S
Usami
D000293:Adolescent; D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D023061:Gene Order; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017434:Protein Structure, Tertiary; D055815:Young Adult; D015044:Zona Pellucida / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; C491350:TECTA protein, human