Jean-Christophe Leclère1, Marie-Suzanne Le Gac1, Cedric Le Maréchal2, Claude Ferec2, Rémi Marianowski3. 1. Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital CHU Brest, France. 2. Genetic Department, University Hospital CHU Brest, France. 3. Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital CHU Brest, France. Electronic address: r.marianowski@free.fr.
Abstract
OBJECTIVES: To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with GJB2 mutations. DESIGN: Case series. SETTING: Collaborative study in referral centers, institutional practice. PATIENTS: A total of 690 hearing-impaired patients were genotypically and phenotypically described. The mutations of GJB2 and GJB6 were studied. Heterozygous patients were searched for another mutation by microsatellite approach. MAIN OUTCOME MEASURES: Prevalence of GJB2 mutations, microsatellite approach, hearing-impairment. RESULTS: In 498 patients (72,17% of the cohort), no mutation was found. Homozygotous patients were 59 (8,55%), with 51 for c.35delG, 6 for p.M34T and 2 for GJB6. Compound heterozygous were 64 (9,28%) with 56 c.35delG-others mutations. Genotypes with biallelic non sense mutations had a high risk of severe to profound hearing impairment. It was frequently milder in compound heterozygotes than in c.35delG homozygotes. Heterozygous patients were 69 (10%) with 21 c.35delG, 20 p.M34T and 28 others mutations. We selected patients with a complete historical medical file (clinical and audiometric data). Then, we performed a microsatellite approach (multiplex PCR of short DNA fragments) to localize a new pathologic allele. Seventeen heterozygous patients were studied. Six patients (35%) showed the same haplotype. They were compound heterozygous bearing a new pathologic allele. CONCLUSION: Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness. A new haplotype for GJB2 is described but the exact mutation remains unknown.
OBJECTIVES: To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with GJB2 mutations. DESIGN: Case series. SETTING: Collaborative study in referral centers, institutional practice. PATIENTS: A total of 690 hearing-impairedpatients were genotypically and phenotypically described. The mutations of GJB2 and GJB6 were studied. Heterozygous patients were searched for another mutation by microsatellite approach. MAIN OUTCOME MEASURES: Prevalence of GJB2 mutations, microsatellite approach, hearing-impairment. RESULTS: In 498 patients (72,17% of the cohort), no mutation was found. Homozygotous patients were 59 (8,55%), with 51 for c.35delG, 6 for p.M34T and 2 for GJB6. Compound heterozygous were 64 (9,28%) with 56 c.35delG-others mutations. Genotypes with biallelic non sense mutations had a high risk of severe to profound hearing impairment. It was frequently milder in compound heterozygotes than in c.35delG homozygotes. Heterozygous patients were 69 (10%) with 21 c.35delG, 20 p.M34T and 28 others mutations. We selected patients with a complete historical medical file (clinical and audiometric data). Then, we performed a microsatellite approach (multiplex PCR of short DNA fragments) to localize a new pathologic allele. Seventeen heterozygous patients were studied. Six patients (35%) showed the same haplotype. They were compound heterozygous bearing a new pathologic allele. CONCLUSION: Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness. A new haplotype for GJB2 is described but the exact mutation remains unknown.
Authors: Leila Youssefian; Hassan Vahidnezhad; Amir Hossein Saeidian; Hamidreza Mahmoudi; Razieh Karamzadeh; Ariana Kariminejad; Jianhe Huang; Leping Li; Thomas F Jannace; Paolo Fortina; Sirous Zeinali; Thomas W White; Jouni Uitto Journal: Hum Mutat Date: 2018-12-01 Impact factor: 4.878