title: Comorbidity of GJB2 and WFS1 mutations in one family.
abstract: It is rarely reported that two distinct genetic mutations affecting hearing have been found in one family. We report on a family exhibiting comorbid mutation of GJB2 and WFS1. A four-generation Japanese family with autosomal dominant sensorineural hearing loss was studied. In 7 of the 24 family members, audiometric evaluations and genetic analysis were performed. We detected A-to-C nucleotide transversion (c.2576G>C) in exon 8 of WFS1 that was predicted to result in an arginine-to-proline substitution at codon 859 (R859P), G-to-A transition (c.109G>A) in exon 2 of GJB2 that was predicted to result in a valine-to-isoleucine substitution at codon 37 (V37I), and C-to-T transition (c.427C>T) in exon 2 of GJB2 that was predicted to result in an arginine-to-tryptophan substitution at codon 143 (R143W). Two individuals who had heterozygosity of GJB2 mutations and heterozygosity of WFS1 mutations showed low-frequency hearing loss. One individual who had homozygosity of GJB2 mutation without WFS1 mutation had moderate, gradual high tone hearing loss. On the other hand, a moderate flat loss configuration was seen in one individual who had compound heterozygosity of GJB2 and heterozygosity of WFS1 mutations. Our results indicate that the individual who has both GJB2 and WFS1 mutations can show GJB2 phenotype.
authors.affiliation: NHO Tokyo Medical Center, Department of Otolaryngology, Japan. shujirominami@me.com
authors.forename: Shujiro B
authors.initials: SB
authors.lastname: Minami
authors.forename: Sawako
authors.initials: S
authors.lastname: Masuda
authors.forename: Satoko
authors.initials: S
authors.lastname: Usui
authors.forename: Hideki
authors.initials: H
authors.lastname: Mutai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005091:Exons; D005260:Female; D034381:Hearing Loss / Q000235:genetics; D006320:Hearing Tests; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C114987:wolframin protein; D000072259:Connexin 26