Genetic Factors in Birth Defects

已经确定了大约20个重大畸形，可供未来调查。 从先天性畸形登记处沿着选择具有主要出生缺陷的病例以及合适的对照受试者。 来自登记处的数据已与该州的新生儿筛查计划联系起来，以确定用于DNA提取的滤纸样本。已经为许多项目选择了样本并提取了DNA。 第一批报告已经完成，并已提交出版。 目前正在审查两项。 此外，其他三个项目的基因分型现已完成，即先天性腹股沟疝、肢体缺陷和胎儿酒精综合征。 对这些数据的分析正在进行中。 其他项目的样本正在鉴定、进行DNA提取或进行单核苷酸多态性（SNP）基因分型。 第一批完成的项目是脐膨出和先天性巨结肠。 脐膨出调查发现，成为病例与转钴胺素2（维生素B12）受体基因之间存在关联。 如果得到证实，这一发现表明B12可能有助于预防脐膨出，也可以解释以前的工作，即母亲使用多种维生素与脐膨出风险降低之间的关联。这项研究还发现了与同型半胱氨酸代谢相关的其他基因与脐膨出之间的暗示性关联。 这些发现表明同型半胱氨酸代谢（与维生素B12有关）可能与脐膨出有因果关系。 第二个完成的项目检查了与神经组织迁移和先天性巨结肠症相关的基因。 通过测序发现了先前报道的与先天性巨结肠相关的基因RET的新变体。 还发现了其他参与迁移的潜在重要基因。 目前正在继续开展工作，以查明病例，并从DNA库中获取样本进行DNA提取。 还正在审查数据，以确定通过不同方法进行研究的罕见缺陷。 将通过大规模阵列分析DNA以鉴定拷贝数变异。

Approximately 20 major malformations have been identified for future investigations. Cases with the major birth defects of interest have been selected from the Congenital Malformations Registry along with suitable control subjects. Data from the Registry have been linked with the state's Newborn Screening Program to identify filter paper samples for DNA extraction. Samples have been selected and DNA has been extracted for many projects. The first reports have been completed and have been submitted for publication. Two are currently under review. In addition genotyping is now complete for three other projects, congenital diaphragmatic hernia, limb defects, and fetal alcohol syndrome. Analysis of these data is underway. Samples for other projects are being identified, undergoing DNA extraction, or being genotyped for single nucleotide polymorphisms (SNPs. The first completed projects are on omphalocele and Hirschsprung's disease. The omphalocele investigation found an association between being a case and the transcobalamin 2 (vitamin B12) receptor gene. If confirmed, this finding suggests that B12 may be useful in preventing omphaloceles and may also explain previous work that showed an association between maternal multivitamin use and reduced risk for omphalocele. This study also found a suggestive association between other genes related to homocysteine metabolism and omphalocele. These findings suggest that homocysteine metabolism (which is related to vitamin B12) could be causally related to omphalocele. The second completed project examined genes related to migration of neural tissue and Hirschsprung's disease. New variants of a gene previously reported to be related to Hirschsprung's disease,RET, were found by sequencing. Other potentially important genes involved in migration were also found. Work is continuing to identify cases and obtain samples from the bank for DNA extraction. Data are also being reviewed to identify rare defects for study by a different approach. DNA will be analyzed by large scale arrays to identify copy number variants.