caa a22 4500 606185380 CHVBK 20210128100831.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00405-014-3157-5 doi (NATIONALLICENCE)springer-10.1007/s00405-014-3157-5 Identification and genotype/phenotype correlation of mutations in a large German cohort with hearing loss [Elektronische Daten] [Christopher Beck, Jose Pérez-Álvarez, Alexander Sigruener, Frank Haubner, Till Seidler, Charalampos Aslanidis, Jürgen Strutz, Gerd Schmitz] The prevalence of hearing impairment is estimated as approximately 1 on 1,000 newborn children. To assess a higher mutation detection rate in individuals with hearing loss a three-step mutation screening program consisting of GJB2 in first line, then GJB1, GJB3 and GJB6 (second step) and if tested negative or heterozygote, testing of GJA1, GJB4, SLC26A4 and PJVK (third) was performed. Audiograms were derived from all patients to characterize audiological features of GJB2 mutations especially. In 59 patients (31.3%) of the 188 probands, the hearing impairment was due to GJB2 mutations, 45 (23.9%) of these being homozygous for 35delG mutation and 14 (7.4%) compound heterozygous for GJB2 mutations in the coding region of exon 2 whereas no significant sequence variation was found in exon 1. In 22 (11.7%) additional patients a single recessive mutation in GJB2, GJB3, GJB6 and SLC26A4 without a second mutation on the other allele was identified, making genetic counseling difficult. Our study showed significant difference in hearing loss degree in the patients with GJB2-mutations. Forty-five (45.5%) GJB2-cases were identified in 99 individuals diagnosed with severe to profound hearing loss, 14 (17.7%) GJB2-cases were identified in 79 individuals with moderate deafness whereas no clear GJB2 mutation was found in 10 patients with mild hearing loss (p<0.001). Revealing a high variability of hearing levels in identical genotypes (even intrafamilial), a significant genotype-phenotype correlation could not be established. Based on the identified mutations spectrum and frequencies, speaking mostly of GJB2, a step by step screening for mutations can be devised and in addition may lead to a better stratification of patients for specific therapeutical approaches. Springer-Verlag Berlin Heidelberg, 2014 Non-syndromic nationallicence Deafness nationallicence GJB2 nationallicence Genotype nationallicence Phenotype nationallicence Mutation nationallicence Beck Christopher Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut Pérez-Álvarez Jose Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut Sigruener Alexander Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut Haubner Frank Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut Seidler Till Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut Aslanidis Charalampos Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut Strutz Jürgen Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut Schmitz Gerd Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/10(2015-10-01), 2765-2776 0937-4477 272:10<2765 2015 272 405 https://doi.org/10.1007/s00405-014-3157-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00405-014-3157-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Beck Christopher Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut NATIONALLICENCE 700 1- Pérez-Álvarez Jose Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut NATIONALLICENCE 700 1- Sigruener Alexander Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut NATIONALLICENCE 700 1- Haubner Frank Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut NATIONALLICENCE 700 1- Seidler Till Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut NATIONALLICENCE 700 1- Aslanidis Charalampos Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut NATIONALLICENCE 700 1- Strutz Jürgen Institute for Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany aut NATIONALLICENCE 700 1- Schmitz Gerd Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany aut NATIONALLICENCE 773 0- European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/10(2015-10-01), 2765-2776 0937-4477 272:10<2765 2015 272 405