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Its etiology is considered to be heterogenous, including both genetic and environmental factors that remain largely unknown. To further elucidate the genetic cause in a five\u2010generation Goldenhar syndrome pedigree and exploit the whole\u2010exome sequencing (WES) data of this pedigree, we generated collapsed haplotype pattern markers based on WES and employed rare variant nonparametric linkage analysis.\n                    <jats:italic>FBLN2<\/jats:italic>\n                    was identified as a candidate gene via analysis of WES data across the significant linkage region. A\n                    <jats:italic>fbln2<\/jats:italic>\n                    knockout zebrafish line was established by CRISPR\/Cas9 to examine the gene's role in craniofacial cartilage development.\n                    <jats:italic>fbln2<\/jats:italic>\n                    was expressed specifically in the mandible during the zebrafish early development, while\n                    <jats:italic>fbln2<\/jats:italic>\n                    knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that\n                    <jats:italic>fbln2<\/jats:italic>\n                    knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the bone morphogenic protein (BMP) signaling pathway in the zebrafish model. This study demonstrates the role of\n                    <jats:italic>FBLN2<\/jats:italic>\n                    in CNCC development and BMP pathway regulation, and highlights\n                    <jats:italic>FBLN2<\/jats:italic>\n                    as a candidate gene for Goldenhar syndrome, which may have implications for the selection of potential screening targets and the development of treatments for conditions like microtia\u2010atresia.\n                  <\/jats:p>","DOI":"10.1111\/nyas.15183","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T11:20:41Z","timestamp":1720264841000},"page":"113-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<i>FBLN2<\/i>\n                    is associated with Goldenhar syndrome and is essential for cranial neural crest cell development"],"prefix":"10.1111","volume":"1537","author":[{"given":"Xiaomin","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9671-6553","authenticated-orcid":false,"given":"Fuyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"8\u2010Year MD Program Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing People's Republic of 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