Byrne J, Cama A, Reilly M, Vigliarolo M, Levato L, Boni L, Lavia N, Andreussi L
Boyne Research Institute, Drogheda, Ireland.
Am J Med Genet. 1996 Dec 18;66(3):303-10. doi: 10.1002/(SICI)1096-8628(19961218)66:3<303::AID-AJMG13>3.0.CO;2-Q.
Periconceptional vitamin supplementation with folate prevents about three-quarters of expected cases of neural tube defects (NTDs) in clinical trials. However, vitamin action may be regulated at the level of the gene, and individual susceptibility to environmental agents, including dietary components, also may be under genetic control. We investigated the presence of familial factors in a retrospective case control study of neural tube defects in Genoa, Italy. Cases included all patients treated at a single pediatric neurosurgical service. Controls matched on age and sex came from the same hospital. We found strong evidence for the contribution of genetic factors in this study. There was an excess risk of 14 for the occurrence of NTDs in first-degree relatives compared to controls (P < .0005). There was no difference in sex ratio in any group of relatives, but maternal grandparents of children with a high spinal lesion had 14% fewer off-spring than paternal grandparents (P < .005), possibly because of excess miscarriages. Our study is the first to show complex patterns of inheritance in spina bifida families affecting three generation in one clinical subgroup and preferentially on the mother's side. These results support a role for genomic imprinting and highlight the value of multidisciplinary epidemiologic and clinical studies that include multiple generations. New studies incorporating dietary and genetic approaches will help clarify and extend these findings.
在临床试验中，受孕前补充叶酸维生素可预防约四分之三预期的神经管缺陷（NTD）病例。然而，维生素的作用可能在基因水平上受到调控，而且个体对包括饮食成分在内的环境因素的易感性也可能受基因控制。我们在意大利热那亚进行的一项神经管缺陷回顾性病例对照研究中调查了家族因素的存在情况。病例包括在单一儿科神经外科接受治疗的所有患者。年龄和性别匹配的对照来自同一家医院。我们在这项研究中发现了基因因素起作用的有力证据。与对照组相比，一级亲属中发生神经管缺陷的风险高出14倍（P < 0.0005）。任何亲属组中的性别比例均无差异，但患有高位脊柱病变儿童的外祖父母的孙辈比祖父母的孙辈少14%（P < 0.005），这可能是由于流产过多所致。我们的研究首次表明，脊柱裂家族存在复杂的遗传模式，在一个临床亚组中影响三代人，且优先影响母系。这些结果支持了基因组印记的作用，并突出了包括多代人的多学科流行病学和临床研究的价值。纳入饮食和基因方法的新研究将有助于阐明和扩展这些发现。
