Kaur Maninder, DeScipio Cheryl, McCallum Jennifer, Yaeger Dinah, Devoto Marcella, Jackson Laird G, Spinner Nancy B, Krantz Ian D
Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Am J Med Genet A. 2005 Sep 15;138(1):27-31. doi: 10.1002/ajmg.a.30919.
The Cornelia de Lange syndrome (CdLS) (OMIM# 122470) is a dominantly inherited multisystem developmental disorder. The phenotype consists of characteristic facial features, hirsutism, abnormalities of the upper extremities ranging from subtle changes in the phalanges and metacarpal bones to oligodactyly and phocomelia, gastroesophageal dysfunction, growth retardation, and neurodevelopmental delay. Prevalence is estimated to be as high as 1 in 10,000. Recently, mutations in NIPBL were identified in sporadic and familial CdLS cases. To date, mutations in this gene have been identified in over 45% of individuals with CdLS. NIPBL is the human homolog of the Drosophila Nipped-B gene. Although its function in mammalian systems has not yet been elucidated, sequence homologs of Nipped-B in yeast (Scc2 and Mis4) are required for sister chromatid cohesion during mitosis, and a similar role was recently demonstrated for Nipped-B in Drosophila. In order to evaluate NIPBL role in sister chromatid cohesion in humans, metaphase spreads on 90 probands (40 NIPBL mutation positive and 50 NIPBL mutation negative) with CdLS were evaluated for evidence of precocious sister chromatid separation (PSCS). We screened 50 metaphases from each proband and found evidence of PSCS in 41% (compared to 9% in control samples). These studies indicate that NIPBL may play a role in sister chromatid cohesion in humans as has been reported for its homologs in Drosophila and yeast.
科妮莉亚·德朗热综合征（CdLS）（OMIM编号：122470）是一种显性遗传的多系统发育障碍。其表型包括特征性面部特征、多毛症、上肢异常，范围从指骨和掌骨的细微变化到多指畸形和短肢畸形、胃食管功能障碍、生长发育迟缓以及神经发育延迟。据估计，患病率高达万分之一。最近，在散发性和家族性CdLS病例中发现了NIPBL基因的突变。迄今为止，在超过45%的CdLS患者中已鉴定出该基因的突变。NIPBL是果蝇Nipped - B基因的人类同源物。尽管其在哺乳动物系统中的功能尚未阐明，但酵母中Nipped - B的序列同源物（Scc2和Mis4）在有丝分裂期间姐妹染色单体黏附中是必需的，最近在果蝇中也证明了Nipped - B具有类似作用。为了评估NIPBL在人类姐妹染色单体黏附中的作用，对90名CdLS先证者（40名NIPBL突变阳性和50名NIPBL突变阴性）的中期染色体铺展进行了评估，以寻找早熟姐妹染色单体分离（PSCS）的证据。我们从每个先证者中筛选了50个中期染色体，发现41%存在PSCS证据（相比之下，对照样本中为9%）。这些研究表明，NIPBL可能在人类姐妹染色单体黏附中发挥作用，正如其在果蝇和酵母中的同源物所报道的那样。
