Borck Guntram, Zarhrate Mohamed, Bonnefont Jean-Paul, Munnich Arnold, Cormier-Daire Valérie, Colleaux Laurence
INSERM U781 and Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
Hum Mutat. 2007 Feb;28(2):205-6. doi: 10.1002/humu.9478.
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.
科妮莉亚·德朗热综合征（CdLS）是一种多系统发育障碍，其特征为面部畸形、生长和智力发育迟缓、小头畸形以及各种畸形。在约45%的受影响个体中检测到NIPBL基因的杂合突变。最近，已鉴定出第二个CdLS基因，定位于X染色体：SMC1L1（类染色体结构维持蛋白1；或SMC1A）。为了估计X连锁型CdLS的发病率并完善其临床表现，我们筛查了一系列11名未携带NIPBL异常的CdLS男孩。我们鉴定出两个新的SMC1L1错义突变（c.587G>A [p.Arg196His]和c.3254A>G [p.Tyr1085Cys]）。我们的结果证实SMC1L1突变可导致CdLS，并支持SMC1L1导致相当一部分原因不明的CdLS男孩患病的观点。此外，我们认为SMC1L1突变在产前和产后生长发育迟缓及相关畸形方面的影响比NIPBL突变更为轻微。如果得到证实，这些数据可能对指导CdLS的突变筛查具有重要意义。
