{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:33:54Z","timestamp":1774676034036,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2014_A14"],"award-info":[{"award-number":["2014_A14"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE 1723\/1\u20101"],"award-info":[{"award-number":["RE 1723\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,4,17]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Syndromic brain malformations comprise a large group of anomalies with a birth prevalence of about 1 in 1,000 live births. Their etiological factors remain largely unknown. To identify causative mutations, we used whole\u2010exome sequencing (WES) in aborted fetuses and children with syndromic brain malformations in which chromosomal microarray analysis was previously unremarkable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>WES analysis was applied in eight case\u2010parent trios, six aborted fetuses, and two children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES identified a novel <jats:italic>de novo<\/jats:italic> mutation (p.Gly268Arg) in <jats:italic>ACTB<\/jats:italic> (Baraitser\u2010Winter syndrome\u20101), a homozygous stop mutation (p.R2442*) in <jats:italic>ASPM<\/jats:italic> (primary microcephaly type 5), and a novel hemizygous X\u2010chromosomal mutation (p.I250V) in <jats:italic>SLC9A6<\/jats:italic> (X\u2010linked syndromic mentaly retardation, Christianson type). Furthermore, WES identified a <jats:italic>de novo mutation<\/jats:italic> (p.Arg1093Gln) in <jats:italic>BAZ1A<\/jats:italic>. This mutation was previously reported in only one allele in 121.362 alleles tested (dbSNP build 147). <jats:italic>BAZ1A<\/jats:italic> has been associated with neurodevelopmental impairment and dysregulation of several pathways including vitamin D metabolism. Here, serum vitamin\u2010D (25\u2010(OH)D) levels were insufficient and gene expression comparison between the child and her parents identified 27 differentially expressed genes. Of note, 10 out of these 27 genes are associated to cytoskeleton, integrin and synaptic related pathways, pinpointing to the relevance of <jats:italic>BAZ1A<\/jats:italic> in neural development. <jats:italic>In situ<\/jats:italic> hybridization in mouse embryos between E10.5 and E13.5 detected <jats:italic>Baz1a<\/jats:italic> expression in the central and peripheral nervous system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In syndromic brain malformations, WES is likely to identify causative mutations when chromosomal microarray analysis is unremarkable. Our findings suggest <jats:italic>BAZ1A<\/jats:italic> as a possible new candidate gene.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1200","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T05:16:40Z","timestamp":1517462200000},"page":"587-597","source":"Crossref","is-referenced-by-count":26,"title":["Exome sequencing in syndromic brain malformations identifies novel mutations in <i>ACTB<\/i>, and <i>SLC9A6<\/i>, and suggests <i>BAZ1A<\/i> as a new candidate gene"],"prefix":"10.1002","volume":"110","author":[{"given":"Valerie","family":"Weitensteiner","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Bonn School of Medicine and University Hospital of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn School of Medicine and University Hospital of Bonn Bonn Germany"},{"name":"Department of Genomics\u2014Life &amp; 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