title: Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.
abstract: Mutations in WFS1 are reported to be responsible for two conditions with distinct phenotypes; DFNA6/14/38 and autosomal recessive Wolfram syndrome. They differ in their associated symptoms and inheritance mode, and although their most common clinical symptom is hearing loss, it is of different types. While DNFA6/14/38 is characterized by low frequency sensorineural hearing loss (LFSNHL), in contrast, Wolfram syndrome is associated with various hearing severities ranging from normal to profound hearing loss that is dissimilar to LFSNHL (Pennings et al. 2002). To confirm whether within non-syndromic hearing loss patients WFS1 mutations are found restrictively in patients with LFSNHL and to summarize the mutation spectrum of WFS1 found in Japanese, we screened 206 Japanese autosomal dominant and 64 autosomal recessive (sporadic) non-syndromic hearing loss probands with various severities of hearing loss. We found three independent autosomal dominant families associated with two different WFS1 mutations, A716T and E864K, previously detected in families with European ancestry. Identification of the same mutations in independent families with different racial backgrounds suggests that both sites are likely to be mutational hot spots. All three families with WFS1 mutations in this study showed a similar phenotype, LFSNHL, as in previous reports. In this study, one-third (three out of nine) autosomal dominant LFSNHL families had mutations in the WFS1 gene, indicating that in non-syndromic hearing loss WFS1 is restrictively and commonly found within autosomal dominant LFSNHL families.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Hisakuni
authors.initials: H
authors.lastname: Fukuoka
authors.affiliation: Kanda ENT Clinic, 4-25 Wakakusa-cho, Nagasaki, 852-8023, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Aomori Prefectural Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori, 030-8553, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ohta
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; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D014929:Wolfram Syndrome / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein