Pavlina Plevova1, Martina Paprskarova, Petra Tvrda, Petra Turska, Rastislav Slavkovsky, Eva Mrazkova. 1. *Department of Medical Genetics, University Hospital of Ostrava †Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc ‡Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
Abstract
OBJECTIVE: This study aimed to clarify the molecular epidemiology of hearing loss by identifying the responsible genes in patients without GJB2 mutations. STUDY DESIGN: Prospective genetic study. SETTING: Tertiary referral hospital. PATIENTS: Fifty one patients with bilateral sensorineural hearing loss, 20 men, and 31 women, mean age 24.9 years, range 3 to 64 years, from 49 families. GJB2 and deltaGJB6-D13S1830 mutations were excluded previously. INTERVENTION: Diagnostic. Sixty-nine genes reported to be causative of hearing loss were analyzed. Sequence capture technology, next-generation sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used. Coverage of STRC was screened in Integrative Genomics Viewer software. MAIN OUTCOME MEASURE: Identification of causal pathogenic mutations in genes related to deafness. RESULTS: Five families (10%) had recessive STRC deletions or mutations. Five unrelated patients (10%) had recessive mutations in TMPRSS3, USH2A, PCDH15, LOXHD1, and MYO15A. Three families (6%) had autosomal dominant mutations in MYO6A, KCNQ4, and SIX1. One family (2%) had an X-linked POU3F4 mutation. Thus, we identified the cause of hearing loss in 28% of the families studied. CONCLUSIONS: Following GJB2, STRC was the second most frequently mutated gene in patients from the Czech Republic with hearing loss. To decrease the cost of testing, we recommend STRC deletion screening with MLPA before next-generation sequencing. The existence of a pseudogene and polymorphic STRC regions can lead to false-positive or false-negative results when copy number variation analysis is based on next-generation sequencing data.
OBJECTIVE: This study aimed to clarify the molecular epidemiology of hearing loss by identifying the responsible genes in patients without GJB2 mutations. STUDY DESIGN: Prospective genetic study. SETTING: Tertiary referral hospital. PATIENTS: Fifty one patients with bilateral sensorineural hearing loss, 20 men, and 31 women, mean age 24.9 years, range 3 to 64 years, from 49 families. GJB2 and deltaGJB6-D13S1830 mutations were excluded previously. INTERVENTION: Diagnostic. Sixty-nine genes reported to be causative of hearing loss were analyzed. Sequence capture technology, next-generation sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used. Coverage of STRC was screened in Integrative Genomics Viewer software. MAIN OUTCOME MEASURE: Identification of causal pathogenic mutations in genes related to deafness. RESULTS: Five families (10%) had recessive STRC deletions or mutations. Five unrelated patients (10%) had recessive mutations in TMPRSS3, USH2A, PCDH15, LOXHD1, and MYO15A. Three families (6%) had autosomal dominant mutations in MYO6A, KCNQ4, and SIX1. One family (2%) had an X-linked POU3F4 mutation. Thus, we identified the cause of hearing loss in 28% of the families studied. CONCLUSIONS: Following GJB2, STRC was the second most frequently mutated gene in patients from the Czech Republic with hearing loss. To decrease the cost of testing, we recommend STRC deletion screening with MLPA before next-generation sequencing. The existence of a pseudogene and polymorphic STRC regions can lead to false-positive or false-negative results when copy number variation analysis is based on next-generation sequencing data.
Authors: Guney Bademci; Clemer Abad; Armagan Incesulu; Abolfazl Rad; Ozgul Alper; Susanne M Kolb; Filiz B Cengiz; Oscar Diaz-Horta; Fatma Silan; Ercan Mihci; Emre Ocak; Maryam Najafi; Reza Maroofian; Elanur Yilmaz; Banu G Nur; Duygu Duman; Shengru Guo; David W Sant; Gaofeng Wang; Paula V Monje; Thomas Haaf; Susan H Blanton; Barbara Vona; Katherina Walz; Mustafa Tekin Journal: Hum Genet Date: 2018-07-07 Impact factor: 4.132
Authors: Anke Tropitzsch; Thore Schade-Mann; Philipp Gamerdinger; Saskia Dofek; Björn Schulte; Martin Schulze; Florian Battke; Sarah Fehr; Saskia Biskup; Andreas Heyd; Marcus Müller; Hubert Löwenheim; Barbara Vona; Martin Holderried Journal: Ear Hear Date: 2022 May/Jun Impact factor: 3.562