title: Homozygosity for the V37I GJB2 mutation in fifteen probands with mild to moderate sensorineural hearing impairment: further confirmation of pathogenicity and haplotype analysis in Asian populations.
abstract: Hearing impairment affects 1 in 650 newborns, making it the most common congenital sensory impairment. Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing impairment cases. Mutations in GJB2 account for a significant number of ARNSHI (and up to 50% of documented recessive (e.g., more than 1 affected sibling) hearing impairment in some populations). Mutations in the GJB2 gene are amongst the most common causes of hearing impairment in populations of various ethnic backgrounds. Two mutations of this gene, 35delG and 167delT, account for the majority of reported mutations in Caucasian populations, especially those of Mediterranean and Ashkenazi Jewish background. The 235delC mutation is most prevalent in East Asian populations. Some mutations are of less well-characterized significance. The V37I missense mutation, common in Asian populations, was initially described as a polymorphism and later as a potentially pathogenic mutation. We report here on 15 unrelated individuals with ARNSHI and homozygosity for the V37I GJB2 missense mutation. Nine individuals are of Chinese ancestry, two are of unspecified Asian descent, one is of Japanese descent, one individual is of Vietnamese ancestry, one of Philippine background and one of Italian and Cuban/Caucasian background. Homozygosity for the V37I GJB2 mutation may be a more common pathogenic missense mutation in Asian populations, resulting in mild to moderate sensorineural hearing impairment. We report a presumed haplotype block specific to East Asian individuals with the V37I mutation encompassing the GJB2 gene that may account for the high prevalence in East Asian populations.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Gallant
authors.forename: Lauren
authors.initials: L
authors.lastname: Francey
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Tsai
authors.forename: Micah
authors.initials: M
authors.lastname: Berman
authors.forename: Yaru
authors.initials: Y
authors.lastname: Zhao
authors.forename: Heather
authors.initials: H
authors.lastname: Fetting
authors.forename: Maninder
authors.initials: M
authors.lastname: Kaur
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.forename: Alisha
authors.initials: A
authors.lastname: Wilkens
authors.forename: Dinah
authors.initials: D
authors.lastname: Clark
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003062:Codon; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D003062:Codon; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: China; GJB2; V37I; haplotype; hearing impairment