{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:07:51Z","timestamp":1777370871561,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T00:00:00Z","timestamp":1387411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Wolf\u2013Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the distal 4p chromosome, characterized by craniofacial features, growth impairment, intellectual disability, and seizures. Although genotype\u2013phenotype correlation studies have previously been published, several important issues remain to be elucidated including seizure severity. We present detailed clinical and molecular\u2010cytogenetic findings from a microarray and fluorescence in situ hybridization (FISH)\u2010based genotype\u2013phenotype analysis of 22 Japanese WHS patients, the first large non\u2010Western series. 4p deletions were terminal in 20 patients and interstitial in two, with deletion sizes ranging from 2.06 to 29.42\u2009Mb. The new Wolf\u2013Hirschhorn syndrome critical region (WHSCR2) was deleted in all cases, and duplication of other chromosomal regions occurred in four. Complex mosaicism was identified in two cases: two different 4p terminal deletions; a simple 4p terminal deletion and an unbalanced translocation with the same 4p breakpoint. Seizures began in infancy in 33% (2\/6) of cases with small (&lt;6\u2009Mb) deletions and in 86% (12\/14) of cases with larger deletions (&gt;6\u2009Mb). Status epilepticus occurred in 17% (1\/6) with small deletions and in 87% (13\/15) with larger deletions. Renal hypoplasia or dysplasia and structural ocular anomalies were more prevalent in those with larger deletions. A new susceptible region for seizure occurrence is suggested between 0.76 and 1.3\u2009Mb from 4pter, encompassing <jats:italic>CTBP1<\/jats:italic> and <jats:italic>CPLX1<\/jats:italic>, and distal to the previously\u2010supposed candidate gene <jats:italic>LETM1<\/jats:italic>. The usefulness of bromide therapy for seizures and additional clinical features including hypercholesterolemia are also described. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36308","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T20:15:29Z","timestamp":1387484129000},"page":"597-609","source":"Crossref","is-referenced-by-count":31,"title":["Microarray and FISH\u2010based genotype\u2013phenotype analysis of 22 Japanese patients with Wolf\u2013Hirschhorn syndrome"],"prefix":"10.1002","volume":"164","author":[{"given":"Kenji","family":"Shimizu","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Shinshu University School of Medicine Matsumoto Japan"},{"name":"Division of Medical Genetics Saitama Children's Medical Center Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Wakui","sequence":"additional","affiliation":[{"name":"Department of Medical 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