{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:10:32Z","timestamp":1769526632002,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 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.<\/jats:p>","DOI":"10.3390\/genes11111329","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T20:20:33Z","timestamp":1605126033000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0037-9079","authenticated-orcid":false,"given":"Julia","family":"Doll","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-3447","authenticated-orcid":false,"given":"Barbara","family":"Vona","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"},{"name":"T\u00fcbingen Hearing Research Centre, Department of Otolaryngology-Head and Neck Surgery, Eberhard Karls University, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-1702","authenticated-orcid":false,"given":"Linda","family":"Schnapp","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5640-810X","authenticated-orcid":false,"given":"Franz","family":"R\u00fcschendorf","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Bacha Khan University Charsadda, Khyber Pakhtunkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-8917","authenticated-orcid":false,"given":"Sher","family":"Alam Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamed","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajmal","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bacha Khan University Charsadda, Khyber Pakhtunkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naseer","family":"Ahmad","sequence":"additional","affiliation":[{"name":"District Eye Specialist, Police and Services Hospital Peshawar, Khyber Pakhtunkkhwa 24420, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne M.","family":"Kolb","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-8681","authenticated-orcid":false,"given":"Laura","family":"K\u00fchlewein","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eberhard Karls University, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D. J.","family":"Labonne","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence C.","family":"Layman","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela A. H.","family":"Hofrichter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tabea","family":"R\u00f6der","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Dittrich","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"},{"name":"Department of Bioinformatics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler D.","family":"Graves","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5567-1088","authenticated-orcid":false,"given":"Il-Keun","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Division of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indrajit","family":"Nanda","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung-Goo","family":"Kim","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, 34110 Doha, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-0763","authenticated-orcid":false,"given":"Thomas","family":"Haaf","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12687-011-0072-y","article-title":"Consanguineous marriages: Preconception consultation in primary health care settings","volume":"3","author":"Hamamy","year":"2012","journal-title":"J. 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