Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-219293
- The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with anThe current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.…
Autor(en): | Julia DollORCiD, Barbara VonaORCiD, Linda SchnappORCiD, Franz Rüschendorf, Imran Khan, Saadullah Khan, Noor Muhammad, Sher Alam Khan, Hamed Nawaz, Ajmal Khan, Naseer Ahmad, Susanne M. Kolb, Laura Kühlewein, Jonathan D. J. Labonne, Lawrence C. Layman, Michaela A. H. Hofrichter, Tabea Röder, Marcus Dittrich, Tobias Müller, Tyler D. Graves, Il-Keun Kong, Indrajit Nanda, Hyung-Goo Kim, Thomas HaafORCiD |
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URN: | urn:nbn:de:bvb:20-opus-219293 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Humangenetik |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Genes |
ISSN: | 2073-4425 |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 11 |
Heft / Ausgabe: | 11 |
Aufsatznummer: | 1329 |
Originalveröffentlichung / Quelle: | Genes 2020, 11(11), 1329; https://doi.org/10.3390/genes11111329 |
DOI: | https://doi.org/10.3390/genes11111329 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Pakistan; consanguinity; exome sequencing; genetic diagnosis; genome-wide linkage analysis; hearing loss |
Datum der Freischaltung: | 09.02.2021 |
Datum der Erstveröffentlichung: | 11.11.2020 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |