{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:05:04Z","timestamp":1774519504114,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2022,5]]},"DOI":"10.1007\/s11033-022-07245-z","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T15:04:55Z","timestamp":1647529495000},"page":"3949-3954","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco"],"prefix":"10.1007","volume":"49","author":[{"given":"Imane","family":"AitRaise","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghita","family":"Amalou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amale","family":"Bousfiha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hicham","family":"Charoute","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Rouba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houria","family":"Abdelghaffar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystel","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Petit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-0281","authenticated-orcid":false,"given":"Adbelhamid","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"7245_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.2471\/BLT.19.224683","volume":"97","author":"BO Olusanya","year":"2019","unstructured":"Olusanya BO, Davis AC, Hoffman HJ (2019) Hearing loss: rising prevalence and impact. Bull World Health Organ 97:646\u2013646. https:\/\/doi.org\/10.2471\/BLT.19.224683. A","journal-title":"Bull World Health Organ"},{"key":"7245_CR2","doi-asserted-by":"publisher","first-page":"E2382","DOI":"10.3390\/ijms21072382","volume":"21","author":"S-H Wong","year":"2020","unstructured":"Wong S-H, Yen Y-C, Li S-Y, Yang J-J (2020) Novel Mutations in the TMPRSS3 Gene may Contribute to Taiwanese Patients with Nonsyndromic Hearing Loss. Int J Mol Sci 21:E2382. https:\/\/doi.org\/10.3390\/ijms21072382","journal-title":"Int J Mol Sci"},{"key":"7245_CR3","doi-asserted-by":"publisher","first-page":"E1233","DOI":"10.3390\/genes11101233","volume":"11","author":"P Buonfiglio","year":"2020","unstructured":"Buonfiglio P, Bruque CD, Luce L et al (2020) GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort. Genes 11:E1233. https:\/\/doi.org\/10.3390\/genes11101233","journal-title":"Genes"},{"key":"7245_CR4","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ejmg.2016.05.002","volume":"59","author":"A Bakhchane","year":"2016","unstructured":"Bakhchane A, Bousfiha A, Charoute H et al (2016) Update of the spectrum of GJB2 gene mutations in 152 Moroccan families with autosomal recessive nonsyndromic hearing loss. Eur J Med Genet 59:325\u2013329. https:\/\/doi.org\/10.1016\/j.ejmg.2016.05.002","journal-title":"Eur J Med Genet"},{"key":"7245_CR5","doi-asserted-by":"publisher","first-page":"11011","DOI":"10.1007\/s11033-012-2003-3","volume":"39","author":"M Charif","year":"2012","unstructured":"Charif M, Bounaceur S, Abidi O et al (2012) The c.242G>A mutation in LRTOMT gene is responsible for a high prevalence of deafness in the Moroccan population. Mol Biol Rep 39:11011\u201311016. https:\/\/doi.org\/10.1007\/s11033-012-2003-3","journal-title":"Mol Biol Rep"},{"key":"7245_CR6","doi-asserted-by":"publisher","first-page":"e0176516","DOI":"10.1371\/journal.pone.0176516","volume":"12","author":"A Bakhchane","year":"2017","unstructured":"Bakhchane A, Charif M, Bousfiha A et al (2017) Novel compound heterozygous MYO7A mutations in Moroccan families with autosomal recessive non-syndromic hearing loss. PLoS ONE 12:e0176516. https:\/\/doi.org\/10.1371\/journal.pone.0176516","journal-title":"PLoS ONE"},{"key":"7245_CR7","doi-asserted-by":"publisher","first-page":"17009","DOI":"10.1038\/hgv.2017.9","volume":"4","author":"A Bousfiha","year":"2017","unstructured":"Bousfiha A, Bakhchane A, Charoute H et al (2017) A novel PEX1 mutation in a Moroccan family with Zellweger spectrum disorders. Hum Genome Var 4:17009. https:\/\/doi.org\/10.1038\/hgv.2017.9","journal-title":"Hum Genome Var"},{"key":"7245_CR8","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s11033-017-4129-9","volume":"44","author":"A Bousfiha","year":"2017","unstructured":"Bousfiha A, Bakhchane A, Charoute H et al (2017) Novel compound heterozygous mutations in the GPR98 (USH2C) gene identified by whole exome sequencing in a Moroccan deaf family. Mol Biol Rep 44:429\u2013434. https:\/\/doi.org\/10.1007\/s11033-017-4129-9","journal-title":"Mol Biol Rep"},{"key":"7245_CR9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.gene.2015.07.075","volume":"574","author":"A Bakhchane","year":"2015","unstructured":"Bakhchane A, Charoute H, Nahili H et al (2015) A novel mutation in the TMC1 gene causes non-syndromic hearing loss in a Moroccan family. Gene 574:28\u201333. https:\/\/doi.org\/10.1016\/j.gene.2015.07.075","journal-title":"Gene"},{"key":"7245_CR10","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.gene.2013.03.123","volume":"523","author":"M Charif","year":"2013","unstructured":"Charif M, Bakhchane A, Abidi O et al (2013) Analysis of CLDN14 gene in deaf Moroccan patients with non-syndromic hearing loss. Gene 523:103\u2013105. https:\/\/doi.org\/10.1016\/j.gene.2013.03.123","journal-title":"Gene"},{"key":"7245_CR11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ijporl.2017.07.024","volume":"101","author":"S Salime","year":"2017","unstructured":"Salime S, Charif M, Bousfiha A et al (2017) Homozygous mutations in PJVK and MYO15A genes associated with non-syndromic hearing loss in Moroccan families. Int J Pediatr Otorhinolaryngol 101:25\u201329. https:\/\/doi.org\/10.1016\/j.ijporl.2017.07.024","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"7245_CR12","doi-asserted-by":"publisher","first-page":"110481","DOI":"10.1016\/j.ijporl.2020.110481","volume":"140","author":"G Amalou","year":"2021","unstructured":"Amalou G, Bonnet C, Riahi Z et al (2021) A homozygous MPZL2 deletion is associated with non syndromic hearing loss in a moroccan family. Int J Pediatr Otorhinolaryngol 140:110481. https:\/\/doi.org\/10.1016\/j.ijporl.2020.110481","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"7245_CR13","volume-title":"GeneReviews\u00ae","author":"AE Shearer","year":"2017","unstructured":"Shearer AE, Hildebrand MS, Smith RJ (2017) Hereditary Hearing Loss and Deafness Overview. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews\u00ae. University of Washington, Seattle, Seattle (WA)"},{"key":"7245_CR14","doi-asserted-by":"publisher","first-page":"21104","DOI":"10.1073\/pnas.1012989107","volume":"107","author":"AE Shearer","year":"2010","unstructured":"Shearer AE, DeLuca AP, Hildebrand MS et al (2010) Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proc Natl Acad Sci U S A 107:21104\u201321109. https:\/\/doi.org\/10.1073\/pnas.1012989107","journal-title":"Proc Natl Acad Sci U S A"},{"key":"7245_CR15","doi-asserted-by":"publisher","first-page":"W252","DOI":"10.1093\/nar\/gku340","volume":"42","author":"M Biasini","year":"2014","unstructured":"Biasini M, Bienert S, Waterhouse A et al (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42:W252\u2013258. https:\/\/doi.org\/10.1093\/nar\/gku340","journal-title":"Nucleic Acids Res"},{"key":"7245_CR16","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/prot.22570","volume":"9","author":"E Krieger","year":"2009","unstructured":"Krieger E, Joo K, Lee J et al (2009) Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8. Proteins 77 Suppl 9:114\u2013122. https:\/\/doi.org\/10.1002\/prot.22570","journal-title":"Proteins 77 Suppl"},{"key":"7245_CR17","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1093\/bioinformatics\/btu426","volume":"30","author":"E Krieger","year":"2014","unstructured":"Krieger E, Vriend G (2014) YASARA View - molecular graphics for all devices - from smartphones to workstations. Bioinforma Oxf Engl 30:2981\u20132982. https:\/\/doi.org\/10.1093\/bioinformatics\/btu426","journal-title":"Bioinforma Oxf Engl"},{"key":"7245_CR18","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/bioinformatics\/btt691","volume":"30","author":"DEV Pires","year":"2014","unstructured":"Pires DEV, Ascher DB, Blundell TL (2014) mCSM: predicting the effects of mutations in proteins using graph-based signatures. Bioinforma Oxf Engl 30:335\u2013342. https:\/\/doi.org\/10.1093\/bioinformatics\/btt691","journal-title":"Bioinforma Oxf Engl"},{"key":"7245_CR19","doi-asserted-by":"publisher","first-page":"W229","DOI":"10.1093\/nar\/gkx439","volume":"45","author":"AP Pandurangan","year":"2017","unstructured":"Pandurangan AP, Ochoa-Monta\u00f1o B, Ascher DB, Blundell TL (2017) SDM: a server for predicting effects of mutations on protein stability. Nucleic Acids Res 45:W229\u2013W235. https:\/\/doi.org\/10.1093\/nar\/gkx439","journal-title":"Nucleic Acids Res"},{"key":"7245_CR20","doi-asserted-by":"publisher","first-page":"W314","DOI":"10.1093\/nar\/gku411","volume":"42","author":"DEV Pires","year":"2014","unstructured":"Pires DEV, Ascher DB, Blundell TL (2014) DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach. Nucleic Acids Res 42:W314\u2013319. https:\/\/doi.org\/10.1093\/nar\/gku411","journal-title":"Nucleic Acids Res"},{"key":"7245_CR21","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1021\/acs.jcim.8b00697","volume":"59","author":"H Cao","year":"2019","unstructured":"Cao H, Wang J, He L et al (2019) DeepDDG: Predicting the Stability Change of Protein Point Mutations Using Neural Networks. J Chem Inf Model 59:1508\u20131514. https:\/\/doi.org\/10.1021\/acs.jcim.8b00697","journal-title":"J Chem Inf Model"},{"key":"7245_CR22","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1089\/gte.2008.0063","volume":"12","author":"O Abidi","year":"2008","unstructured":"Abidi O, Boulouiz R, Nahili H et al (2008) Carrier frequencies of mutations\/polymorphisms in the connexin 26 gene (GJB2) in the Moroccan population. Genet Test 12:569\u2013574. https:\/\/doi.org\/10.1089\/gte.2008.0063","journal-title":"Genet Test"},{"key":"7245_CR23","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/humu.1156","volume":"18","author":"C Hamelmann","year":"2001","unstructured":"Hamelmann C, Amedofu GK, Albrecht K et al (2001) Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana. Hum Mutat 18:84\u201385. https:\/\/doi.org\/10.1002\/humu.1156","journal-title":"Hum Mutat"},{"key":"7245_CR24","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1017\/S0022215116008689","volume":"130","author":"L Shi","year":"2016","unstructured":"Shi L, Chen J, Li J et al (2016) Prevalence of GJB2 gene mutation in 330 cochlear implant patients in the Jiangsu province. J Laryngol Otol 130:902\u2013906. https:\/\/doi.org\/10.1017\/S0022215116008689","journal-title":"J Laryngol Otol"},{"key":"7245_CR25","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s00405-016-4229-5","volume":"274","author":"A Pavithra","year":"2017","unstructured":"Pavithra A, Chandru J, Jeffrey JM et al (2017) Rare compound heterozygosity involving dominant and recessive mutations of GJB2 gene in an assortative mating hearing impaired Indian family. Eur Arch Oto-Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol -. Head Neck Surg 274:119\u2013125. https:\/\/doi.org\/10.1007\/s00405-016-4229-5","journal-title":"Head Neck Surg"},{"key":"7245_CR26","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.retram.2016.01.005","volume":"64","author":"L Boualla","year":"2016","unstructured":"Boualla L, Jdioui W, Soulami K et al (2016) Clinical and molecular findings in three Moroccan families with distal renal tubular acidosis and deafness: Report of a novel mutation of ATP6V1B1 gene. Curr Res Transl Med 64:5\u20138. https:\/\/doi.org\/10.1016\/j.retram.2016.01.005","journal-title":"Curr Res Transl Med"},{"key":"7245_CR27","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/mgg3.205","volume":"4","author":"LI Escobar","year":"2016","unstructured":"Escobar LI, Simian C, Treard C et al (2016) Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families. Mol Genet Genomic Med 4:303\u2013311. https:\/\/doi.org\/10.1002\/mgg3.205","journal-title":"Mol Genet Genomic Med"},{"key":"7245_CR28","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/1471-2350-14-119","volume":"14","author":"D Elhayek","year":"2013","unstructured":"Elhayek D, Perez de Nanclares G, Chouchane S et al (2013) Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes. BMC Med Genet 14:119. https:\/\/doi.org\/10.1186\/1471-2350-14-119","journal-title":"BMC Med Genet"},{"key":"7245_CR29","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/cge.12919","volume":"92","author":"C Fallerini","year":"2017","unstructured":"Fallerini C, Baldassarri M, Trevisson E et al (2017) Alport syndrome: impact of digenic inheritance in patients management. Clin Genet 92:34\u201344. https:\/\/doi.org\/10.1111\/cge.12919","journal-title":"Clin Genet"},{"key":"7245_CR30","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1681\/ASN.V12197","volume":"12","author":"L Heidet","year":"2001","unstructured":"Heidet L, Arrondel C, Forestier L et al (2001) Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome. J Am Soc Nephrol JASN 12:97\u2013106","journal-title":"J Am Soc Nephrol JASN"},{"key":"7245_CR31","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/humu.23206","volume":"38","author":"S Issa","year":"2017","unstructured":"Issa S, Bondurand N, Faubert E et al (2017) EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state. Hum Mutat 38:581\u2013593. https:\/\/doi.org\/10.1002\/humu.23206","journal-title":"Hum Mutat"},{"key":"7245_CR32","doi-asserted-by":"publisher","unstructured":"Li W, Mei L, Chen H et al (2019) New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing. Neural Plast 2019:7143458. https:\/\/doi.org\/10.1155\/2019\/7143458","DOI":"10.1155\/2019\/7143458"},{"key":"7245_CR33","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.anl.2017.03.022","volume":"45","author":"N Morimoto","year":"2018","unstructured":"Morimoto N, Mutai H, Namba K et al (2018) Homozygous EDNRB mutation in a patient with Waardenburg syndrome type 1. Auris Nasus Larynx 45:222\u2013226. https:\/\/doi.org\/10.1016\/j.anl.2017.03.022","journal-title":"Auris Nasus Larynx"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-022-07245-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-022-07245-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-022-07245-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T16:27:24Z","timestamp":1654619244000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-022-07245-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["7245"],"URL":"https:\/\/doi.org\/10.1007\/s11033-022-07245-z","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-814770\/v1","asserted-by":"object"}]},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]},"assertion":[{"value":"23 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The genetic study was approved by the medical ethics committee of the Morocco Pasteur Institute.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from legal guardians.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Patients signed informed consent regarding publishing their data.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}