{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:00:34Z","timestamp":1791327634993,"version":"4.3.1"},"reference-count":36,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2009,11,24]]},"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Holoprosencephaly (HPE), the most common malformation of the human forebrain, may be due to mutations in genes associated with non-syndromic HPE. Mutations in <jats:italic>ZIC2<\/jats:italic>, located on chromosome 13q32, are a common cause of non-syndromic, non-chromosomal HPE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To characterise genetic and clinical findings in patients with <jats:italic>ZIC2<\/jats:italic> mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Through the National Institutes of Health and collaborating centres, DNA from approximately 1200 individuals with HPE spectrum disorders was analysed for sequence variations in <jats:italic>ZIC2<\/jats:italic>. Clinical details were examined and all other known cases of mutations in <jats:italic>ZIC2<\/jats:italic> were included through a literature search.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>By direct sequencing of DNA samples of an unselected group of unrelated patients with HPE in our NIH laboratory, <jats:italic>ZIC2<\/jats:italic> mutations were found in 8.4% (49\/582) of probands. A total of 157 individuals from 119 unrelated kindreds are described, including 141 patients with intragenic sequence determined mutations in <jats:italic>ZIC2<\/jats:italic>. Only 39\/157 patients have previously been clinically described. Unlike HPE due to mutations in other genes, most mutations occur de novo and the distribution of HPE types differs significantly from that of non-<jats:italic>ZIC2<\/jats:italic> related HPE. Evidence is presented for the presence of a novel facial phenotype which includes bitemporal narrowing, upslanting palpebral fissures, a short nose with anteverted nares, a broad and well demarcated philtrum, and large ears.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HPE due to <jats:italic>ZIC2<\/jats:italic> mutations is distinct from that due to mutations in other genes. This may shed light on the mechanisms involved in formation of the forebrain and face and will help direct genetic counselling and diagnostic strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.073049","type":"journal-article","created":{"date-parts":[[2009,12,2]],"date-time":"2009-12-02T23:07:45Z","timestamp":1259795265000},"page":"513-524","source":"Crossref","is-referenced-by-count":71,"title":["Mutations in <i>ZIC2<\/i> in human holoprosencephaly: description of a Novel <i>ZIC2<\/i> specific phenotype and comprehensive analysis of 157 individuals"],"prefix":"10.1136","volume":"47","author":[{"given":"Benjamin 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