期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 21, 期 11, 页码 1308-1311出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2013.43
关键词
Wilson disease; genetic epidemiology; consanguinity; homozygosity index
资金
- CHERISH project
- Unita Operativa di Genetica Medica, Policlinico Sant'Orsola Malpighi, Bologna, Italy
Wilson disease (WD) is an autosomal recessive disorder resulting in pathological progressive copper accumulation in liver and other tissues. The worldwide prevalence (P) is about 30/million, while in Sardinia it is in the order of 1/10 000. However, all of these estimates are likely to suffer from an underdiagnosis bias. Indeed, a recent molecular neonatal screening in Sardinia reported a WD prevalence of 1:2707. In this study, we used a new approach that makes it possible to estimate the allelic frequency (q) of an autosomal recessive disorder if one knows the proportion between homozygous and compound heterozygous patients (the homozygosity index or HI) and the inbreeding coefficient (F) in a sample of affected individuals. We applied the method to a set of 178 Sardinian individuals (3 of whom born to consanguineous parents), each with a clinical and molecular diagnosis of WD. Taking into account the geographical provenance of the parents of every patient within Sardinia (to make F computation more precise), we obtained a q = 0.0191 (F = 7.8 x 10(-4), HI = 0.476) and a corresponding prevalence P = 1:2732. This result confirms that the prevalence of WD is largely underestimated in Sardinia. On the other hand, the general reliability and applicability of the HI approach to other autosomal recessive disorders is confirmed, especially if one is interested in the genetic epidemiology of populations with high frequency of consanguineous marriages.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据