Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome
Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome
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DOI：
10.1002/ajmg.a.31305
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发表时间：
2006-07-15
影响因子：
2
通讯作者：
Wierzba, Jolanta
中科院分区：
文献类型：
--
作者：
Yan, Jiong;Saifi, Gulam Mustafa;Wierzba, Jolanta
科尔内利亚德兰格综合征（CdLS）是一种多系统先天性异常疾病，以产前和产后生长迟缓、发育迟缓、面部畸形、肢体畸形和多器官缺陷为特征。最近发现NIPBL基因突变是该综合征的主要病因，在27-56%的患者中检测到。两组研究发现，突变阳性和突变阴性患者的某些表型的严重程度或异常率有显著差异。在错义突变与截短突变患者中也描述了不同的临床特征。在这项研究中，我们在28名无关的波兰CdLS患者（46.4%）中发现了13个NIPBL突变，其中11个是新的。与突变阴性个体相比，突变阳性患者在出生时的体重、身高和平均头围、面部畸形和语言障碍方面受到更严重的影响。对本研究和之前两项研究的综合数据进行分析后发现，生长、发育迟缓和肢体缺陷的程度在有突变和无突变的患者之间以及错义突变和截短突变的患者之间存在显著差异，而在任何单独的研究中，这些特征中只有一部分存在显著差异。此外，NIPBL蛋白的生物信息学分析揭示了几个新的结构域，这可能会提供进一步的线索，这种蛋白的潜在功能。(c)2006 Wiley-Liss，Inc.
Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by prenatal and postnatal growth retardation, developmental delay, distinctive facial dysmorphism, limb malformations, and multiple organ defects. Mutations in the NIPBL gene have been discovered recently as a major etiology for this syndrome, and were detected in 27-56% of patients. Two groups have found significant differences in the severity or penetrance of some phenotypes between mutation positive and mutation negative patients. Different clinical features have also been described among patients with missense versus truncating mutations. In this study, we identified 13 NIPBL mutations in 28 unrelated Polish CdLS patients (46.4%), 11 were novel. Mutation positive patients were more severely affected in comparison to mutation negative individuals with respect to weight, height, and mean head circumference at birth, facial dysmorphism and speech impairment. Analyses of combined data from this and the two previous studies revealed that the degree of growth, developmental delay and limb defects showed significant differences between patients with and without mutations and between patients with missense and truncating mutations, whereas only a portion of these features differed significantly in any individual Study. Furthermore, bioinformatic analyses of the NIPBL protein revealed several novel domains, which may give further clues about potential functions of this protein. (c) 2006 Wiley-Liss, Inc.