{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:55:04Z","timestamp":1788497704175,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Jordan Deanship of Scientific Research","award":["2238"],"award-info":[{"award-number":["2238"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>SLC26A4 is one of the most common genes causing autosomal recessive non-syndromic sensorineural hearing loss (SNHL). It has been reported to cause Pendred Syndrome (PDS) and DFNB4 which is deafness with enlarged vestibular aqueduct (EVA). However, mutated SLC26A4 is not conclusive for having either DFNB4 or PDS. Three unrelated Jordanian families consisting of eight affected individuals with congenital bilateral hearing loss (HL) participated in this study. Whole-exome and Sanger sequencing were performed to investigate the underlying molecular etiology of HL. Further clinical investigations, including laboratory blood workup for the thyroid gland, CT scan for the temporal bone, and thyroid ultrasound were performed. Three disease-causing variants were identified in SLC26A4 in the three families, two of which were novel. Two families had a novel pathogenic homozygous splice-site accepter variant (c.165-1G&gt;C), while the third family had compound heterozygous pathogenic variants (c.1446G&gt;A; p.Trp482* and c.304G&gt;A; p.Gly102Arg). Our approach helped in redirecting the diagnosis of several affected members of three different families from non-syndromic HL to syndromic HL. Two of the affected individuals had typical PDS, one had DFNB4, while the rest had atypical PDS. Our work emphasized the intra- and inter-familial variability of SLC26A4-related phenotypes. In addition, we highlighted the variable phenotypic impact of SLC26A4 on tailoring a personalized healthcare management.<\/jats:p>","DOI":"10.3390\/genes13122192","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T01:46:56Z","timestamp":1669254416000},"page":"2192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["SLC26A4 Phenotypic Variability Influences Intra- and Inter-Familial Diagnosis and Management"],"prefix":"10.3390","volume":"13","author":[{"given":"Mohamed","family":"Tawalbeh","sequence":"first","affiliation":[{"name":"Department of Special Surgery, Jordan University Hospital, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunia","family":"Aburizeg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayan O.","family":"Abu Alragheb","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wala Sami","family":"Alaqrabawi","sequence":"additional","affiliation":[{"name":"Hearing and Speech Department, School of Rehabilitation Sciences, The University of Jordan, Amman 11942, Jordan"},{"name":"Audiology Department, Faculty of Medical Sciences, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain","family":"Dardas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-4455","authenticated-orcid":false,"given":"Luma","family":"Srour","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baraah Hatem","family":"Altarayra","sequence":"additional","affiliation":[{"name":"King Hussein Cancer Center, Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman A.","family":"Zayed","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Jordan University Hospital, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid","family":"El Omari","sequence":"additional","affiliation":[{"name":"Otolaryngology, Head and Neck Surgery Department, Jordanian Royal Medical Services, Amman 11855, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-6489","authenticated-orcid":false,"given":"Bilal","family":"Azab","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"},{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","first-page":"57","article-title":"Pendred Syndrome Is Caused by Mutations in a Putative Sulphate Transporter Gene (PDS)","volume":"15","author":"Everett","year":"1997","journal-title":"Nat. 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