title: Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.
abstract: The present study of KCNQ4 mutations was carried out to 1) determine the prevalence by unbiased population-based genetic screening, 2) clarify the mutation spectrum and genotype/phenotype correlations, and 3) summarize clinical characteristics. In addition, a review of the reported mutations was performed for better understanding of this deafness gene. The screening using 287 probands from unbiased Japanese autosomal dominant nonsyndromic hearing loss (ADNSHL) families identified 19 families with 7 different disease causing mutations, indicating that the frequency is 6.62% (19/287). While the majority were private mutations, one particular recurrent mutation, c.211delC, was observed in 13 unrelated families. Haplotype analysis in the vicinity of c.211delC suggests existence of a common ancestor. The majority of the patients showed all frequency, but high-frequency predominant, sensorineural hearing loss. The present study adds a new typical audiogram configuration characterized by mid-frequency predominant hearing loss caused by the p.V230E mutation. A variant at the N-terminal site (c. 211delC) showed typical ski-slope type audiogram configuration. Concerning clinical features, onset age was from 3 to 40 years old, and mostly in the teens, and hearing loss was gradually progressive. Progressive nature is a common feature of patients with KCNQ4 mutations regardless of the mutation type. In conclusion, KCNQ4 mutations are frequent among ADNSHL patients, and therefore screening of the gene and molecular confirmation of these mutations have become important in the diagnosis of these conditions.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Naito
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Nishio
authors.forename: Yoh-ichiro
authors.initials: Y
authors.lastname: Iwasa
authors.forename: Takuya
authors.initials: T
authors.lastname: Yano
authors.forename: Kozo
authors.initials: K
authors.lastname: Kumakawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Abe
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kojima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Namba
authors.forename: Chie
authors.initials: C
authors.lastname: Oshikawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Usami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018703:Founder Effect; D056726:Genetic Association Studies; D005820:Genetic Testing; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010898:Pitch Perception; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human