CDKN1C (p57Kip2) Analysis in Beckwith-Wiedemann Syndrome (BWS) Patients: Genotype-Phenotype Correlations, Novel Mutations, and Polymorphisms
CDKN1C (p57Kip2) Analysis in Beckwith-Wiedemann Syndrome (BWS) Patients: Genotype-Phenotype Correlations, Novel Mutations, and Polymorphisms
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DOI：
10.1002/ajmg.a.33453
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发表时间：
2010-06-01
影响因子：
2
通讯作者：
Lapunzina, Pablo
中科院分区：
文献类型：
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作者：
Romanelli, Valeria;Belinchon, Alberta;Lapunzina, Pablo
beckwithwithwiedemann综合征（BWS）是一种以大舌、大儿和腹壁缺陷为特征的过度生长综合征。它是一种多基因疾病，在大多数患者中由生长调节基因的改变引起。少数BWS患者（5-10%）有CDKN1C突变，CDKN1C是G1细胞周期蛋白复合物的细胞周期蛋白依赖性激酶抑制剂，作为细胞生长和增殖的负调节因子。在这里，我们报告了8例BWS和CDKN1C突变患者，并回顾了以前报道的病例。我们分析了72例CDKN1C缺陷患者（50例BWS， 17例孤立性半增生（IH）， 3例脐膨出，2例巨漏），目的是寻找新的突变并确定基因型表型相关性。我们的研究结果表明，CDKN1C突变的BWS患者与其他分子缺陷的患者具有不同的临床畸形模式。多指畸形、生殖器异常、乳头外翻和腭裂在CDKN1C突变的BWS中更为常见。这些畸形的临床观察可能有助于决定应该进行哪些遗传鉴定（即CDKN1C筛查），从而优化BWS的实验室评估。(C) 2010 Wiley-Liss, Inc。
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by macroglossia, macrosomia, and abdominal wall defects. It is a multigenic disorder caused in most patients by alterations in growth regulatory genes. A small number of individuals with BWS (5-10%) have mutations in CDKN1C, a cyclin-dependent kinase inhibitor of G1 cyclin complexes that functions as a negative regulator of cellular growth and proliferation. Here, we report on eight patients with BWS and CDKN1C mutations and review previous reported cases. We analyzed 72 patients (50 BWS, 17 with isolated hemi-hyperplasia (IH), three with omphalocele, and two with macroglossia) for CDKN1C defects with the aim to search for new mutations and to define genotype phenotype correlations. Our findings suggest that BWS patients with CDKN1C mutations have a different pattern of clinical malformations than those with other molecular defects. Polydactyly, genital abnormalities, extra nipple, and cleft palate are more frequently observed in BWS with mutations in CDKN1C. The clinical observation of these malformations may help to decide which genetic characterization should be undertaken (i.e., CDKN1C screening), thus optimizing the laboratory evaluation for BWS. (C) 2010 Wiley-Liss, Inc.