{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:04Z","timestamp":1791229624486,"version":"4.1.0"},"reference-count":7,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:00:00Z","timestamp":1444694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS 35129"],"award-info":[{"award-number":["R01 NS 35129"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Exome sequencing identified homozygous loss\u2010of\u2010function variants in <jats:italic>DIAPH1<\/jats:italic> (c.2769delT; p.F923fs and c.3145C&gt;T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early\u2010onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous <jats:italic>DIAPH1<\/jats:italic> mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense <jats:italic>DIAPH1<\/jats:italic> mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of <jats:italic>DIAPH1<\/jats:italic> was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous <jats:italic>DIAPH1<\/jats:italic> mutation. Another homozygous <jats:italic>DIAPH1<\/jats:italic> mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between <jats:italic>DIAPH1<\/jats:italic> mutations and a neurodevelopmental disorder. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37422","type":"journal-article","created":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T03:37:22Z","timestamp":1444793842000},"page":"435-440","source":"Crossref","is-referenced-by-count":48,"title":["Novel loss\u2010of\u2010function variants in <i>DIAPH1<\/i> associated with syndromic microcephaly, blindness, and early onset seizures"],"prefix":"10.1002","volume":"170","author":[{"given":"Almundher","family":"Al\u2010Maawali","sequence":"first","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital Boston Massachusetts"},{"name":"Howard Hughes Medical Institute Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Genetics College of Medicine and Health Sciences Sultan Qaboos University Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda J.","family":"Barry","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital Boston Massachusetts"},{"name":"Howard Hughes Medical Institute Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rajab","sequence":"additional","affiliation":[{"name":"National Genetics Center Directorate General of Health Affairs Ministry of Health Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"El\u2010Quessny","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Seman","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Newton","family":"Coury","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. James","family":"Barkovich","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Radiology Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital Boston Massachusetts"},{"name":"Howard Hughes Medical Institute Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganeshwaran H.","family":"Mochida","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"},{"name":"Manton Center for Orphan Disease Research Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts"},{"name":"Pediatric Neurology Unit Department of Neurology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan M.","family":"Stoler","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Department of Medicine Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-54"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.82"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1315"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-39"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3020"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-302882"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000975107"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37422","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:05:52Z","timestamp":1696622752000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,13]]},"references-count":7,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1002\/ajmg.a.37422"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37422","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,13]]}}}