Goldmuntz E, Driscoll D, Budarf M L, Zackai E H, McDonald-McGinn D M, Biegel J A, Emanuel B S
Department of Pediatrics, Children's Hospital of Philadelphia, PA 19104.
J Med Genet. 1993 Oct;30(10):807-12. doi: 10.1136/jmg.30.10.807.
Congenital conotruncal cardiac defects occur with increased frequency in patients with DiGeorge syndrome (DGS). Previous studies have shown that the majority of patients with DGS or velocardiofacial syndrome (VCFS) have a microdeletion within chromosomal region 22q11. We hypothesised that patients with conotruncal defects who were not diagnosed with DGS or VCFS would also have 22q11 deletions. Seventeen non-syndromic patients with one of three types of conotruncal defects most commonly seen in DGS or VCFS were evaluated for a 22q11 deletion. DNA probes from within the DiGeorge critical region were used. Heterozygosity at a locus was assessed using restriction fragment length polymorphisms. Copy number was determined by dosage analysis using Southern blot analysis of fluorescence in situ hybridisation of metaphase spreads. Five of 17 patients were shown to have a 22q11 deletion when evaluated by dosage analysis. This study shows a genetic contribution to the development of some conotruncal cardiac malformations and alters knowledge regarding the risk of heritability of these defects in certain cases.
先天性圆锥动脉干心脏缺陷在DiGeorge综合征（DGS）患者中出现的频率增加。先前的研究表明，大多数DGS或腭心面综合征（VCFS）患者在染色体区域22q11内存在微缺失。我们假设，未被诊断为DGS或VCFS的圆锥动脉干缺陷患者也会有22q11缺失。对17例患有DGS或VCFS中最常见的三种圆锥动脉干缺陷之一的非综合征患者进行了22q11缺失评估。使用了来自DiGeorge关键区域内的DNA探针。利用限制性片段长度多态性评估一个位点的杂合性。通过中期染色体铺展的Southern印迹分析或荧光原位杂交的剂量分析来确定拷贝数。通过剂量分析评估时，17例患者中有5例显示存在22q11缺失。这项研究表明某些圆锥动脉干心脏畸形的发生存在遗传因素，并改变了关于这些缺陷在某些情况下遗传风险的认识。
