Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients
Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients
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DOI：
10.1038/sj.ejhg.5201737
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发表时间：
2007-02-01
影响因子：
5.2
通讯作者：
Anderlid, Britt Marie
中科院分区：
文献类型：
--
作者：
Schoumans, Jacqueline;Wincent, Josephine;Anderlid, Britt Marie
Cornelia de Lange 综合征（CdLS；OMIM 122470）是一种罕见的多发性先天性异常/智力低下综合征，其特征是独特的畸形面部特征、严重的生长和发育迟缓以及上肢异常。约50%的CdLS患者被发现存在NIPBL基因杂合突变，最近发现少数病例是由X连锁SMC1L1基因突变引起的。我们通过直接测序对瑞典诊断为 CdLS 的 11 名患者（9 名散发病例和 2 名家族病例）的所有 NIPBL 编码外显子进行了突变筛查，并在其中 7 名病例中检测到了突变。所有突变都是从头开始的，其中六种突变以前从未被描述过。随后对四名没有可识别 NIPBL 突变的患者进行多重连接依赖性探针扩增分析，以排除 NIPBL 的整个外显子缺失/重复。此外，还对NIPBL的50个非翻译区（5'UTR）进行了突变分析。对这四名患者进行了平铺分辨率阵列比较基因组杂交分析，以检测隐性染色体失衡，此外还对男孩进行了 SMC1L1 突变筛查。我们在一名具有 CdLS 样表型的患者中发现了大小为 0.6Mb 的从头 9p 重复，但在 SMC1L1 中未检测到突变。到目前为止，已鉴定出两个基因（NIPBL 和 SMC1L1）可引起 CdLS 或 CdLS 样表型。然而，在相当大比例的表现出 CdLS 表型的个体中，没有发现这两个基因中任何一个的突变，并且应考虑包含其他 CdLS 致病基因的其他潜在位点。
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients ( nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 50 untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes ( NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.