Incidence and clinical features of X-linked Cornelia de Lange syndrome due toSMC1L1 mutations

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Borck, Guntram | Zarhrate, Mohamed | Bonnefont, Jean-Paul | Munnich, Arnold | Cormier-Daire, Valérie | Colleaux, Laurence

Edité par CCSD ; Wiley -

International audience. 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.

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