{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:37:48Z","timestamp":1783820268278,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,5,5]],"date-time":"2011-05-05T00:00:00Z","timestamp":1304553600000},"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":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Legius syndrome, is a recently identified autosomal dominant disorder caused by loss of function mutations in the <jats:italic>SPRED1<\/jats:italic> gene, with individuals mainly presenting with multiple caf\u00e9\u2010au\u2010lait macules (CALM), freckling and macrocephaly. So far, only <jats:italic>SPRED1<\/jats:italic> point mutations have been identified as the cause of this syndrome. To determine if copy number changes (CNCs) are a cause of Legius syndrome, we have used a Multiplex Ligation\u2010dependent Probe Amplification (MLPA) assay covering all <jats:italic>SPRED1<\/jats:italic> exons in a cohort of 510 <jats:italic>NF1<\/jats:italic>\u2010negative patients presenting with multiple CALMs with or without freckling, but no other NF1 diagnostic signs. Four different deletions were identified by MLPA and confirmed by quantitative PCR, reverse transcriptase PCR and\/or array CGH: a deletion of exon 1 and the <jats:italic>SPRED1<\/jats:italic> promoter region in a proband and two first\u2010degree relatives; a deletion of the entire <jats:italic>SPRED1<\/jats:italic> gene in a sporadic patient; a deletion of exon 2\u20106 in a proband and her father; and an \u223c6.6\u2009Mb deletion on chromosome 15 that spans <jats:italic>SPRED1<\/jats:italic> in a sporadic patient. Deletions account for \u223c10% of the 40 detected <jats:italic>SPRED1<\/jats:italic> mutations in this cohort of 510 individuals. These results indicate the need for dosage analysis to complement sequencing\u2010based <jats:italic>SPRED1<\/jats:italic> mutation analyses. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33894","type":"journal-article","created":{"date-parts":[[2011,5,5]],"date-time":"2011-05-05T16:55:31Z","timestamp":1304614531000},"page":"1352-1359","source":"Crossref","is-referenced-by-count":15,"title":["Identification of <i>SPRED1<\/i> deletions using RT\u2010PCR, multiplex ligation\u2010dependent probe amplification and quantitative 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