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Incidence and clinical features of X‐linked Cornelia de Lange syndrome due to SMC1L1 mutations
Author(s) -
Borck Guntram,
Zarhrate Mohamed,
Bonnefont JeanPaul,
Munnich Arnold,
CormierDaire Valérie,
Colleaux Laurence
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9478
Subject(s) - cornelia de lange syndrome , microcephaly , biology , missense mutation , genetics , incidence (geometry) , mutation , intellectual disability , developmental disorder , growth retardation , gene , medicine , autism , pregnancy , physics , psychiatry , optics
Abstract Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder characterized by facial dysmorphism, growth and mental retardation, microcephaly, and various malformations. Heterozygous mutations in the NIPBL gene have been detected in approximately 45% of affected individuals. Recently, a second CdLS gene, mapping to the X chromosome, has been identified: SMC1L1 ( structural maintenance of chromosomes 1‐like 1 ; or SMC1A ). In order to estimate the incidence and refine the clinical presentation of X‐linked CdLS, we have screened a series of 11 CdLS boys carrying no NIPBL anomaly. We have identified two novel de novo SMC1L1 missense mutations (c.587G>A [p.Arg196His] and c.3254A>G [p.Tyr1085Cys]). Our results confirm that SMC1L1 mutations cause CdLS and support the view that SMC1L1 accounts for a significant fraction of boys with unexplained CdLS. Furthermore, we suggest that SMC1L1 mutations have milder effects than NIPBL mutations with respect to pre‐ and postnatal growth retardation and associated malformations. If confirmed, these data may have important implications for directing mutation screening in CdLS. © 2007 Wiley‐Liss, Inc.