Zittergruen M M, Murray J C, Lauer R M, Burns T L, Sheffield V C
Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Circulation. 1995 Nov 15;92(10):2803-10. doi: 10.1161/01.cir.92.10.2803.
Congenital heart disease is common in Down syndrome patients, with atrioventricular septal defects accounting for a majority of the abnormalities. The molecular mechanisms of meiotic nondisjunction resulting in Down syndrome were studied for associations with the presence of atrioventricular septal defects.
Twenty highly polymorphic chromosome 21 microsatellite markers were used to genotype two groups of patients (group 1: Down syndrome with atrioventricular septal defects, n = 43; and group 2: Down syndrome without cardiac defects, n = 51) to determine (1) the parental origin of the extra chromosome, (2) the stage of meiotic nondisjunction resulting in the trisomy, (3) the presence or absence of disomic homozygosity or heterozygosity, and (4) the degree of recombination in the nondisjoined chromosomes. The parental origin of the nondisjoined chromosome was maternal in 86.2% of the families, with no significant differences between groups. The most centromeric marker was nonreduced, indicating a meiosis I nondisjunction in 76.5% of maternally derived trisomies, and reduced, indicating a meiosis II nondisjunction in 76.9% of paternally derived trisomies, with no significant differences between groups. There were no significant differences in the proportion of reduced markers at any locus between groups. The distribution of the number of crossovers was significantly different between groups (chi 2 = 14.12, P < .001), with less recombination observed in group 1.
In Down syndrome patients, no association was found between the presence of an atrioventricular septal defect and the parent of origin, stage of meiotic nondisjunction, or disomic homozygosity or heterozygosity. A significant association was found between the presence of an atrioventricular septal defect and reduced frequency of recombination.
先天性心脏病在唐氏综合征患者中很常见，房室间隔缺损占大多数异常情况。研究了导致唐氏综合征的减数分裂不分离的分子机制与房室间隔缺损的存在之间的关联。
使用20个高度多态性的21号染色体微卫星标记对两组患者进行基因分型（第1组：患有房室间隔缺损的唐氏综合征患者，n = 43；第2组：无心脏缺陷的唐氏综合征患者，n = 51），以确定（1）额外染色体的亲本来源，（2）导致三体性的减数分裂不分离阶段，（3）二体纯合性或杂合性的存在与否，以及（4）不分离染色体中的重组程度。不分离染色体的亲本来源在86.2%的家庭中为母系，两组之间无显著差异。最靠近着丝粒的标记未减少，表明76.5%的母系来源三体性中减数分裂I不分离，而减少则表明76.9%的父系来源三体性中减数分裂II不分离，两组之间无显著差异。两组在任何位点的减少标记比例均无显著差异。两组之间交叉数的分布有显著差异（χ2 = 14.12，P <.001），第1组观察到的重组较少。
在唐氏综合征患者中，未发现房室间隔缺损的存在与亲本来源、减数分裂不分离阶段或二体纯合性或杂合性之间存在关联。发现房室间隔缺损的存在与重组频率降低之间存在显著关联。
