{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:04:39Z","timestamp":1791389079699,"version":"4.3.3"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["U01MH127692"],"award-info":[{"award-number":["U01MH127692"]}]},{"name":"National Institute of Health","award":["U01-HG-009716"],"award-info":[{"award-number":["U01-HG-009716"]}]},{"name":"African Academy of Science\/Wellcome Trust","award":["H3A\/18\/001"],"award-info":[{"award-number":["H3A\/18\/001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Waardenburg syndrome (WS) represents a group of genetic conditions characterized by auditory and pigmentation defects. Pathogenic variants in PAX3, MITF, SOX10, EDN3, EDNRB, SNAI2, and KITLG genes have been associated with WS across multiple populations; a comprehensive study of WS in Africa has not yet been reported. We conducted a systematic review of clinical expressions and genetics of WS across Africa. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and the study protocol was registered on PROSPERO, the International Prospective Register of Systematic Reviews (2025 CRD420250655744). A literature search was performed on Google Scholar, PubMed, Scopus, Directory of Open Access Journals (DOAJ), Global Index Medicus, African-Wide Information, ScienceDirect, Connecting Repositories (CORE), and the Web of Science databases. We reviewed a total of 15 articles describing 84 WS cases, which showed no gender bias and a mean age at reporting of 17.5 years. Congenital, sensorineural, and profound hearing loss was described in most cases (66.7%; n = 56\/84). WS type 2 (WS2), with characteristically no dystopia canthorum, is the predominant subtype (36.9%; n = 31\/84). Pathogenic variants in four WS known genes, i.e., PAX3 (13 families), SOX10 (7 families), EDNRB (4 families), and EDN3 (1 family), were reported in Morocco, Tunisia, and South Africa. One candidate gene (PAX8) was described in one family in Ghana. Two non-syndromic hearing loss (NSHL) genes (BDP1 and MYO6) were reported in two separate families in South Africa, suggesting a possible phenotypic expansion. The highest number of WS cases was described in South Africa (38.1%; n = 32\/84) and Tunisia (26.2%; n = 22\/84). Gene variants were missense (27\/43), deletion (7\/43), splicing (5\/43), nonsense (2\/43), indel (1\/43), and duplication (1\/43), chiefly segregating in an autosomal dominant inheritance mode. There was no functional data to support the pathogenicity of putative causative variants. This review showed that WS2 is the most common in Africa. Variants in PAX3 and SOX10 were the predominant genetic causes. This study emphasizes the need to further investigate in-depth clinical characterization, molecular landscape, and the pathobiology of WS in Africa.<\/jats:p>","DOI":"10.3390\/ijms27010127","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:19:26Z","timestamp":1766420366000},"page":"127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetics of Waardenburg Syndrome in Africa: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2994-3761","authenticated-orcid":false,"given":"Elvis Twumasi","family":"Aboagye","sequence":"first","affiliation":[{"name":"Department of Pathology, Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"},{"name":"West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9294-476X","authenticated-orcid":false,"given":"Ramses Peigou","family":"Wonkam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-3162","authenticated-orcid":false,"given":"Carmen","family":"de Kock","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-4895","authenticated-orcid":false,"given":"Collet","family":"Dandara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Platform for Pharmacogenomics Research and Translation Unit (PREMED), South African Medical Research Council, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambroise","family":"Wonkam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"},{"name":"McKusick-Nathans Institute and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/cge.12631","article-title":"Hearing Loss in Waardenburg Syndrome: A Systematic Review","volume":"89","author":"Song","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, H. (2016). Waardenburg Syndrome. Atlas of Genetic Diagnosis and Counseling, Springer.","DOI":"10.1007\/978-1-4614-6430-3_244-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s13023-024-03220-y","article-title":"Deciphering Potential Causative Factors for Undiagnosed Waardenburg Syndrome through Multi-Data Integration","volume":"19","author":"Sun","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","unstructured":"Winters, R., and Masood, S. (2025). Waardenburg Syndrome. StatPearls, StatPearls Publishing."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41434-021-00240-2","article-title":"Genetic Insights, Disease Mechanisms, and Biological Therapeutics for Waardenburg Syndrome","volume":"29","author":"Huang","year":"2022","journal-title":"Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1001\/archderm.1962.01590120016003","article-title":"Waardenbrug\u2019s Syndrome. A Variation of the First Arch Syndrome","volume":"86","author":"Campbell","year":"1962","journal-title":"Arch. Dermatol."},{"key":"ref_7","first-page":"269","article-title":"From Single Nucleotide Substitutions up to Chromosomal Deletions: Genetic Pause of Leucism-Associated Disorders in Animals","volume":"129","author":"Fleck","year":"2016","journal-title":"Berl. Munch. Tierarztl. Wochenschr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/humu.23630","article-title":"Expert Specification of the ACMG\/AMP Variant Interpretation Guidelines for Genetic Hearing Loss","volume":"39","author":"Oza","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sohani, Z.N., Meyre, D., de Souza, R.J., Joseph, P.G., Gandhi, M., Dennis, B.B., Norman, G., and Anand, S.S. (2015). Assessing the Quality of Published Genetic Association Studies in Meta-Analyses: The Quality of Genetic Studies (Q-Genie) Tool. BMC Genet., 16.","DOI":"10.1186\/s12863-015-0211-2"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e011458","DOI":"10.1136\/bmjopen-2016-011458","article-title":"Development of a Critical Appraisal Tool to Assess the Quality of Cross-Sectional Studies (AXIS)","volume":"6","author":"Downes","year":"2016","journal-title":"BMJ Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.jclinepi.2011.11.014","article-title":"Assessing Risk of Bias in Prevalence Studies: Modification of an Existing Tool and Evidence of Interrater Agreement","volume":"65","author":"Hoy","year":"2012","journal-title":"J. Clin. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1097\/IJG.0000000000001676","article-title":"Juvenile Open-Angle Glaucoma with Waardenburg Syndrome: A Case Report","volume":"30","author":"AbdelRahman","year":"2021","journal-title":"J. Glaucoma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1007\/s11033-022-07245-z","article-title":"Genetic Heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB Variants Detected among Hearing Impaired Families in Morocco","volume":"49","author":"AitRaise","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s42003-022-03326-8","article-title":"Exome Sequencing of Families from Ghana Reveals Known and Candidate Hearing Impairment Genes","volume":"5","author":"Wonkam","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dia, Y., Loum, B., Dieng, Y.J.K.B., Diop, J.P.D., Adadey, S.M., Aboagye, E.T., Ba, S.A., Tour\u00e9, A.A., Niang, F., and Diaga Sarr, P. (2023). Childhood Hearing Impairment in Senegal. Genes, 14.","DOI":"10.3390\/genes14030562"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000371590","article-title":"A Novel Mutation in the Endothelin B Receptor Gene in a Moroccan Family with Shah-Waardenburg Syndrome","volume":"6","author":"Doubaj","year":"2015","journal-title":"Mol. Syndr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wonkam, E.T., Chimusa, E., Noubiap, J.J., Adadey, S.M., Fokouo, J.V.F., and Wonkam, A. (2019). GJB2 and GJB6 Mutations in Hereditary Recessive Non-Syndromic Hearing Impairment in Cameroon. Genes, 10.","DOI":"10.3389\/fgene.2019.00841"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10900-014-9942-7","article-title":"Clinical Manifestations of Waardenburg Syndrome in a Male Adolescent in Mali, West Africa","volume":"40","author":"Imperato","year":"2015","journal-title":"J. Community Health"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yalcouy\u00e9, A., Traor\u00e9, O., Tam\u00e9ga, A., Ma\u00efga, A.B., Kan\u00e9, F., Oluwole, O.G., Guinto, C.O., K\u00e9ita, M., Timbo, S.K., and DeKock, C. (2021). Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.726776"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mkaouar, R., Riahi, Z., Marrakchi, J., Mezzi, N., Romdhane, L., Boujemaa, M., Dallali, H., Sayeb, M., Lahbib, S., and Jaouadi, H. (2024). Current Phenotypic and Genetic Spectrum of Syndromic Deafness in Tunisia: Paving the Way for Precision Auditory Health. Front. Genet., 15, Erratum in Front. Genet.\u00a02024, 15, 1437233.","DOI":"10.3389\/fgene.2024.1437233"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.7196\/sajch.672","article-title":"Waardenburg Syndrome in Childhood Deafness in Cameroon","volume":"8","author":"Noubiap","year":"2014","journal-title":"S. Afr. J. Child. Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4103\/0378-6323.18951","article-title":"Waardenburg Syndrome Type 2 in an African Patient","volume":"71","author":"Otman","year":"2005","journal-title":"Indian. J. Dermatol. Venereol. Leprol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ijporl.2017.09.029","article-title":"Novel PAX3 Mutations Causing Waardenburg Syndrome Type 1 in Tunisian Patients","volume":"103","author":"Trabelsi","year":"2017","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Uwibambe, E., Mutesa, L., Muhizi, C., Ncogoza, I., Twumasi Aboagye, E., Dukuze, N., Adadey, S.M., DeKock, C., and Wonkam, A. (2025). Etiologies of Early-Onset Hearing Impairment in Rwanda. Genes, 16.","DOI":"10.3390\/genes16030257"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1093\/hmg\/4.12.2407","article-title":"Mutation of the Endothelin-Receptor B Gene in Waardenburg-Hirschsprung Disease","volume":"4","author":"Till","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/cge.14765","article-title":"The Diverse Genetic Landscape of Hearing Impairment in South African Families","volume":"108","author":"Bharadwaj","year":"2025","journal-title":"Clin. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_29","first-page":"291","article-title":"Waardenburg Syndrome in South Africa. Part II. Is There Founder Effect for Type I?","volume":"66","author":"Kromberg","year":"1984","journal-title":"S. Afr. Med. J."},{"key":"ref_30","first-page":"256","article-title":"Waardenburg Syndrome in South Africa. Part I. An Evaluation of the Clinical Findings in 11 Families","volume":"66","author":"Kromberg","year":"1984","journal-title":"S. Afr. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1017\/S0022215100095736","article-title":"Childhood Deafness in Southern Africa. An Aetiological Survey of 3,064 Deaf Children","volume":"97","author":"Sellars","year":"1983","journal-title":"J. Laryngol. Otol."},{"key":"ref_32","first-page":"811","article-title":"The Aetiology of Partial Deafness in Childhood","volume":"54","author":"Sellars","year":"1978","journal-title":"S. Afr. Med. J."},{"key":"ref_33","first-page":"309","article-title":"Deafness in Black Children Is Southern Africa","volume":"51","author":"Sellars","year":"1977","journal-title":"S. Afr. Med. J."},{"key":"ref_34","first-page":"1193","article-title":"Aetiology of Deafness in White Children in the Cape","volume":"50","author":"Sellars","year":"1976","journal-title":"S. Afr. Med. J."},{"key":"ref_35","first-page":"1135","article-title":"Childhood Deafness in Cape Town","volume":"49","author":"Sellars","year":"1975","journal-title":"S. Afr. Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/hmg\/3.1.197","article-title":"A Splice Junction Mutation in PAX3 Causes Waardenburg Syndrome in a South African Family","volume":"3","author":"Butt","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","first-page":"82","article-title":"The Waardenburg Syndrome in Southern Africa","volume":"64","author":"James","year":"1983","journal-title":"S. Afr. Med. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3928\/0191-3913-19790501-09","article-title":"Waardenburg\u2019s Syndrome: Case Reports in Two Nigerians","volume":"16","author":"Amoni","year":"1979","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_39","first-page":"183","article-title":"Heterogeneity of Waardenburg Syndrome in Kenyan Africans","volume":"4","author":"Hageman","year":"1980","journal-title":"Metab. Pediatr. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S110","DOI":"10.1016\/j.ydbio.2018.05.013","article-title":"Neurocristopathies: New Insights 150 Years after the Neural Crest Discovery","volume":"444","author":"Cerrizuela","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/exd.13856","article-title":"Regulation of Melanocyte Stem Cells in the Pigmentation of Skin and Its Appendages: Biological Patterning and Therapeutic Potentials","volume":"28","author":"Qiu","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s004390000328","article-title":"Transcription Factor Hierarchy in Waardenburg Syndrome: Regulation of MITF Expression by SOX10 and PAX3","volume":"107","author":"Potterf","year":"2000","journal-title":"Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nelms, B.L., and Labosky, P.A. (2010). Transcriptional Control of Neural Crest Development, Morgan & Claypool Life Sciences. Developmental Biology.","DOI":"10.4199\/C00010ED1V01Y201003DEB001"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/ijc.35499","article-title":"SOX10, MITF, and microRNAs: Decoding Their Interplay in Regulating Melanoma Plasticity","volume":"157","author":"Lai","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/hmg\/9.13.1907","article-title":"Interaction among SOX10, PAX3 and MITF, Three Genes Altered in Waardenburg Syndrome","volume":"9","author":"Bondurand","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1172\/JCI524","article-title":"Ontogeny of Endothelins-1 and -3, Their Receptors, and Endothelin Converting Enzyme-1 in the Early Human Embryo","volume":"101","author":"Brand","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s10038-018-0425-z","article-title":"Wnt Signaling Pathway Involvement in Genotypic and Phenotypic Variations in Waardenburg Syndrome Type 2 with MITF Mutations","volume":"63","author":"Wang","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1093\/nar\/gkw010","article-title":"Mechanism and Regulation of the Nonsense-Mediated Decay Pathway","volume":"44","author":"Hug","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/AUD.0000000000001007","article-title":"Ear and Hearing Care Workforce: Current Status and Its Implications","volume":"42","author":"Kamenov","year":"2021","journal-title":"Ear Hear."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/MAO.0000000000004401","article-title":"Access to Ear and Hearing Care Globally: A Survey of Stakeholder Perceptions from the Lancet Commission on Global Hearing Loss","volume":"46","author":"Patterson","year":"2025","journal-title":"Otol. Neurotol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4103\/jmisr.jmisr_3_21","article-title":"Waardenburg Syndrome as a Challenging Experience in Pediatric Cochlear Implantation","volume":"4","author":"Abdelmalak","year":"2021","journal-title":"J. Med. Sci. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000513607","article-title":"A Novel Frameshift Variant of the MITF Gene in a Chinese Family with Waardenburg Syndrome Type 2","volume":"12","author":"Li","year":"2021","journal-title":"Mol. Syndr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e1128","DOI":"10.1002\/mgg3.1128","article-title":"Identification of Six Novel Variants in Waardenburg Syndrome Type II by Next-Generation Sequencing","volume":"8","author":"Ren","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1242\/dev.105445","article-title":"Establishing Neural Crest Identity: A Gene Regulatory Recipe","volume":"142","author":"Bronner","year":"2015","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1086\/522090","article-title":"Deletions at the SOX10 Gene Locus Cause Waardenburg Syndrome Types 2 and 4","volume":"81","author":"Bondurand","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100855","DOI":"10.1016\/j.gim.2023.100855","article-title":"Phenotypic Continuum between Waardenburg Syndrome and Idiopathic Hypogonadotropic Hypogonadism in Humans with SOX10 Variants","volume":"25","author":"Rojas","year":"2023","journal-title":"Genet. Med."},{"key":"ref_57","first-page":"20","article-title":"A Novel SOX10 Nonsense Mutation in a Patient with Kallmann Syndrome and Waardenburg Syndrome","volume":"2021","author":"Wakabayashi","year":"2021","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1101\/gad.1566807","article-title":"Quality Control of Eukaryotic mRNA: Safeguarding Cells from Abnormal mRNA Function","volume":"21","author":"Isken","year":"2007","journal-title":"Genes Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"31","DOI":"10.29245\/2572-9411\/2017\/6.1118","article-title":"Waardenburg Syndrome Expression and Penetrance","volume":"2","author":"Shelby","year":"2017","journal-title":"J. Rare Dis. Res. Treat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e45418","DOI":"10.7554\/eLife.45418","article-title":"Neural Crest-Specific Deletion of Rbfox2 in Mice Leads to Craniofacial Abnormalities Including Cleft Palate","volume":"8","author":"Cibi","year":"2019","journal-title":"Elife"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0378-1119(99)00339-X","article-title":"PAX3 Gene Structure, Alternative Splicing and Evolution","volume":"237","author":"Barber","year":"1999","journal-title":"Gene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s43042-025-00652-4","article-title":"A Novel Noncanonical Splicing Pathogenic Variant in PAX3 Associated with Waardenburg Syndrome Type 1 in an Iranian Family","volume":"26","author":"Soosanabadi","year":"2025","journal-title":"Egypt. J. Med. Hum. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:21:02Z","timestamp":1766420462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010127"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010127","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,22]]}}}