{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:47:11Z","timestamp":1791254831368,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2015,6,29]],"date-time":"2015-06-29T00:00:00Z","timestamp":1435536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Saudi Human Genome Project"},{"DOI":"10.13039\/501100019345","name":"King Salman Center for Disability Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100019345","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Meckel\u2013Gruber syndrome (MKS) is a perinatally lethal disorder characterized by the triad of occipital encephalocele, polydactyly and polycystic kidneys. Typical of other disorders related to defective primary cilium (ciliopathies), MKS is genetically heterogeneous with mutations in a dozen genes to date known to cause the disease. In an ongoing effort to characterize MKS clinically and genetically, we implemented a gene panel and next-generation sequencing approach to identify the causal mutation in 25 MKS families. Of the three families that did not harbor an identifiable causal mutation by this approach, two mapped to a novel disease locus in which whole-exome sequencing revealed the likely causal mutation as a homozygous splicing variant in TMEM107, which we confirm leads to aberrant splicing and nonsense-mediated decay. TMEM107 had been independently identified in two mouse models as a cilia-related protein and mutant mice display typical ciliopathy phenotypes. Our analysis of patient fibroblasts shows marked ciliogenesis defect with an accompanying perturbation of sonic hedgehog signaling, highly concordant with the cellular phenotype in Tmem107 mutants. This study shows that known MKS loci account for the overwhelming majority of MKS cases but additional loci exist including MKS13 caused by TMEM107 mutation.<\/jats:p>","DOI":"10.1093\/hmg\/ddv242","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T00:45:10Z","timestamp":1435625110000},"page":"5211-5218","source":"Crossref","is-referenced-by-count":42,"title":["Identification of a novel MKS locus defined by<i>TMEM107<\/i>mutation"],"prefix":"10.1093","volume":"24","author":[{"given":"Ranad","family":"Shaheen","sequence":"first","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agaadir","family":"Almoisheer","sequence":"additional","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eissa","family":"Faqeih","sequence":"additional","affiliation":[{"name":"Department of Pediatric Subspecialty, Children's Specialized Hospital, King Fahad Medical City, Riyadh 59046, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Babay","sequence":"additional","affiliation":[{"name":"Depatment of Obstetrics and Gynecology, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Monies","sequence":"additional","affiliation":[{"name":"Department of Genetics and"},{"name":"Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Tassan","sequence":"additional","affiliation":[{"name":"Department of Genetics and"},{"name":"Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abouelhoda","sequence":"additional","affiliation":[{"name":"Department of Genetics and"},{"name":"Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesam","family":"Kurdi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Al Mardawi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M.I.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and"},{"name":"Department of Obstetrics and Gynecology, Menoufiya University, Menoufiya, Egypt,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Zain","family":"Seidahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Security Forces Hospital Program, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Alnemer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Alsahan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Sogaty","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, King Fahad General Hospital, Jeddah, Saudi 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