Perche Olivier, Menuet Arnaud, Marcos Mélanie, Liu Luyan, Pâris Arnaud, Utami Kagistia H, Kervran Dominique, Cacheux Valere, Laudier Béatrice, Briault Sylvain
UMR7355, CNRS, Orleans, France; Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France; Genetic Department, Regional Hospital, 14 Avenue de l'Hôpital, 45100 Orleans, France.
Eur J Med Genet. 2013 Nov;56(11):635-41. doi: 10.1016/j.ejmg.2013.07.007. Epub 2013 Sep 4.
7qter deletion syndrome includes prenatal and/or postnatal growth retardation, microcephaly, psychomotor delay or mental retardation and a characteristic dysmorphism. If clinical features are well described, the molecular mechanisms underlying the 7qter deletion syndrome remain unknown. Those deletions usually arise de novo. Here, we describe a young boy with an abnormal phenotype consistent with a 7qter deletion syndrome. High resolution genomic analysis (Affymetrix Human Genome Wide SNP 6.0) revealed a 7q36.3 deletion encompassing NCAPG2, ESYT2, WDR60 and VIPR2, inherited from his asymptomatic father and paternal grandfather. In addition, the patient also harbored a MCPH1 deletion inherited from his healthy mother. Combined NCAPG2 and MCPH1 deletions were correlated with low mRNA levels and protein expression in the patient. MCPH1 and NCAPG2 proteins interaction is known to control chromosome structure and we thus propose that double heterozygosity for null mutations of those two genes of the Condensin II system contribute to mental deficiency with severe microcephaly phenotype.
7q末端缺失综合征包括产前和/或产后生长发育迟缓、小头畸形、精神运动发育迟缓或智力低下以及特征性畸形。尽管临床特征已有详细描述，但7q末端缺失综合征的分子机制仍不清楚。这些缺失通常是新发的。在此，我们描述了一名具有与7q末端缺失综合征相符的异常表型的小男孩。高分辨率基因组分析（Affymetrix人类基因组全基因组SNP 6.0）显示存在一个7q36.3缺失，该缺失包含NCAPG2、ESYT2、WDR60和VIPR2，是从他无症状的父亲和祖父那里遗传而来。此外，该患者还携带了从他健康母亲那里遗传来的MCPH1缺失。NCAPG2和MCPH1的联合缺失与患者体内低水平的mRNA和蛋白表达相关。已知MCPH1和NCAPG2蛋白相互作用可控制染色体结构，因此我们提出，凝聚素II系统这两个基因的无效突变的双重杂合性导致了伴有严重小头畸形表型的智力缺陷。
