title: Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.
abstract: GJB2 alleles containing two cis mutations have been rarely found in non-syndromic hearing loss. Herein, we present a Korean patient with non-syndromic hearing loss caused by the R75Q cis mutation with V37I, which arose de novo in the father and was inherited by the patient. Biochemical coupling and hemichannel permeability assays were performed after molecular cloning and transfection of HEK293T cells. Student's t-tests or analysis of variance followed by Tukey's multiple comparison test was used as statistical analysis. Biochemical coupling was significantly reduced in connexin 26 (Cx26)-R75Q- and Cx26-V37I-transfected cells, with greater extent in Cx26-R75Q and Cx26-R75Q+V37I cells. Interestingly, our patient and his father with the mutations had more residual hearing compared with patients with the dominant mutation alone. Although the difference in hemichannel activity between R75Q alone and R75Q in combination with V37I failed to reach significance, it is of note that there is a possibility that V37I located upstream of R75Q might have the ability to ameliorate R75Q expression. Our study emphasizes the importance of cis mutations with R75Q, as the gene effect of R75Q can be modulated depending on the type of additional mutation.
authors.affiliation: Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: 1] Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea [2] Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jinsei
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000032:analysis / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26