Goldmuntz Elizabeth, Driscoll Deborah A, Emanuel Beverly S, McDonald-McGinn Donna, Mei Minghua, Zackai Elaine, Mitchell Laura E
Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):125-9. doi: 10.1002/bdra.20501.
The phenotype associated with deletion of the 22q11.2 chromosomal region is highly variable, yet little is known about the source of this variability. Cardiovascular anomalies, including tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B, perimembranous ventricular septal defects, and aortic arch anomalies, occur in approximately 75% of individuals with a 22q11.2 deletion.
Data from 343 subjects enrolled in a study of the 22q11.2 deletion syndrome were used to evaluate potential modifiers of the cardiac phenotype in this disorder. Subjects with and without cardiac malformations, and subjects with and without aortic arch anomalies were compared with respect to sex and race. In addition, in the subset of subjects from whom a DNA sample was available, genotypes for variants of four genes that are involved in the folate-homocysteine metabolic pathway and that have been implicated as risk factors for other birth defects were compared. Five variants in four genes were genotyped by heteroduplex or restriction digest assays. The chi-square or Fisher's exact test was used to evaluate the association between the cardiac phenotype and each potential modifier.
The cardiac phenotype observed in individuals with a 22q11.2 deletion was not significantly associated with either sex or race. The genetic variants that were evaluated also did not appear to be associated with the cardiovascular phenotype.
Variation in the cardiac phenotype observed between individuals with a 22q11.2 deletion does not appear to be related to sex, race, or five sequence variants in four folate-related genes that are located outside of the 22q11.2 region.
与22q11.2染色体区域缺失相关的表型具有高度变异性，但对于这种变异性的来源知之甚少。心血管异常，包括法洛四联症、动脉干、B型主动脉弓中断、膜周部室间隔缺损和主动脉弓异常，约75%的22q11.2缺失个体中会出现。
来自一项22q11.2缺失综合征研究的343名受试者的数据用于评估该疾病中心脏表型的潜在修饰因素。比较有和没有心脏畸形的受试者以及有和没有主动脉弓异常的受试者的性别和种族。此外，在可获得DNA样本的受试者子集中，比较了参与叶酸-同型半胱氨酸代谢途径且被认为是其他出生缺陷风险因素的四个基因变体的基因型。通过异源双链或限制性消化测定对四个基因中的五个变体进行基因分型。使用卡方检验或Fisher精确检验来评估心脏表型与每个潜在修饰因素之间的关联。
在22q11.2缺失个体中观察到的心脏表型与性别或种族均无显著关联。所评估的基因变体似乎也与心血管表型无关。
22q11.2缺失个体之间观察到的心脏表型变异似乎与性别、种族或位于22q11.2区域之外的四个叶酸相关基因中的五个序列变体无关。
