Heterotrisomy, a significant contributing factor to ventricular septal defect associated with Down syndrome?
Heterotrisomy, a significant contributing factor to ventricular septal defect associated with Down syndrome?
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DOI：
10.1007/s004390000395
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发表时间：
2000-11-01
期刊：
影响因子：
5.3
通讯作者：
Kessling, AM
中科院分区：
文献类型：
--
作者：
Baptista, MJ;Fairbrother, UL;Kessling, AM
唐氏综合症（DS； 21三体）与多种多样的临床特征相关，其中最常见的是先天性心脏缺陷（CHD）。我们应用分子遗传学技术对DS和CHD患儿21号染色体基因的遗传进行了研究。对99个有退行性痴呆患儿家庭的21号染色体长臂多态性标记进行了分析。其中，60名儿童患有冠心病，39名儿童没有冠心病。异三体是指从三个不同的祖父母那里分别继承一个等位基因。在某些情况下，异三体会涉及到三个不同的等位基因的遗传。异三体区域被定义为在DS儿童的非分离染色体的多态位点上显示保留非分离亲本杂合性的区域。使用多态性非编码标记，我们在DS和室间隔缺损（VSD）患儿中发现了一个一致的9.6 cm的异源三体最小区域（D21S167-HMG14）。将DS和VSD患者与其他所有DS患者（无冠心病或合并冠心病）进行比较，发现DS和VSD患者在该区域的非还原或异源三体显著增加（P=0.006， Fisher精确检验，双尾）。我们假设，该区域的一个或多个基因的异三体是21三体中VSD发病的一个促成因素，可能是通过存在三种不同的特定等位基因，也可能是通过存在特定的等位基因组合。
Down syndrome (DS; trisomy 21) is associated with a wide range of variable clinical features, one of the most common being congenital heart defects (CHD). We used molecular genetic techniques to study the inheritance of genes on chromosome 21 in children with DS and CHD. Polymorphic markers on the long arm of chromosome 21 were analysed in 99 families who had a child with DS. Of these, 60 children had a CHD and 39 children had no CHD. Heterotrisomy describes the inheritance of an allele from each of three different grandparents. In some cases heterotrisomy will involve the inheritance of three different alleles. Heterotrisomic regions were defined as those showing retention of non-disjoining parental heterozygosity at polymorphic loci in the non-disjoined chromosomes of children with DS. Using polymorphic non-coding markers, we identified a consistent 9.6-cM minimum region (D21S167-HMG14) of heterotrisomy in children with DS and ventricular septal defect (VSD). Comparing individuals with DS and VSD to all others with DS (those either with no CHD or with any other CHD combined) shows the individuals with DS and VSD to have significantly more non-reduction or heterotrisomy in this region (P=0.006, Fisher's exact test, two-tailed). We postulate that heterotrisomy for a gene or genes in this region is a contributing factor to the pathogenesis of VSD in trisomy 21 either through the presence of three different specific alleles or through the presence of specific combinations of alleles.