The unusual pattern of hereditary bleeding disorders in the province of Newfoundland and Labrador-Canada's most Eastern Province
The unusual pattern of hereditary bleeding disorders in the province of Newfoundland and Labrador-Canada's most Eastern Province
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DOI：
10.1016/j.transci.2018.10.010
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发表时间：
2018-12-01
影响因子：
1.9
通讯作者：
Boyd, Sarah
中科院分区：
文献类型：
--
作者：
Scully, Mary-Frances;Stoffman, Jayson;Boyd, Sarah
纽芬兰和拉布拉多是加拿大最东部省，具有独特的地形和居住模式。目前的人口是土著因努人、因努伊特人和米克马克人的一小部分创始人口和估计28 000名定居者的后裔。这些定居者来自英格兰西南部和爱尔兰东南部，来到世界上最富有的渔业之一投资和工作。他们定居在海湾、小海湾和远离海岸的岛屿上，这些小定居点被称为外港。这些与世隔绝的社区发展出了不寻常的遗传疾病模式，包括一些极其罕见的遗传性出血性疾病（HBD）的不寻常流行。这项研究的目的是使用我们的省级HBD登记处及时记录这些罕见疾病的患病率。通过审查原始初始诊断凝血结果以确认或反驳每个诊断来验证这些诊断。当可用时，我们还记录了潜在的突变。然后将基于人群的患病率与世界血友病联合会（WFH）全球登记处公布的数据进行比较。结果是惊人的。使用WFH数据，NL甲型血友病、因子V、XI和XIII缺乏症的人均患病率分别比加拿大大陆减去拉布拉多的患病率高2.89、4.54、5.44和9.22倍。轻度血友病A的患病率增加可通过瓦尔2016 Ala突变的奠基者效应来解释。所有严重的FXIII缺陷患者都是c.691-1 G > A突变的纯合子。这些结果表明，NL独特的地理和人口分布导致了遗传漂变，增加了一些罕见因子缺乏症的患病率。这种相对较高的患病率为基因型/表型研究提供了潜在的患者库。
Newfoundland and Labrador (NL), the most eastern province of Canada, is characterized by a unique topography and pattern of settlement. The current population is descended from a small founding population of indigenous Innu, Inuit and Mi'kmaq and an estimated 28,000 settlers. These settlers originated from Southwest England and Southeast Ireland and came to invest and work in one of the world's richest fisheries. They settled in bays, coves and islands off the coast, in small settlements called out-ports. These isolated communities developed unusual patterns of genetic disease including an unusual prevalence of some extremely rare Hereditary Bleeding Disorders (HBD). This study was designed to document the prevalence of these rare disorders, at a snapshot in time, using our provincial HBD registry. These diagnoses were verified by reviewing the original initial diagnostic coagulation results to confirm or refute each diagnosis. When available, we also recorded the underlying mutation. Population based prevalence rates were then compared with data published from the World Federation of Hemophilia (WFH) Global Registry. The results are striking. Using the WFH data the per capita prevalence in NL of Hemophilia A, Factors V, XI, and XIII Deficiency are higher than that of mainland Canada minus Labrador by a factor of 2.89, 4.54, 5.44 and 9.22, respectively. The increased prevalence of mild Hemophilia A is explained by a founder effect of the Val 2016 Ala mutation. All the severe FXIII deficient patients are homozygotes for c.691-1 G > A mutation. These results show that NL's unique geography and population distribution led to a genetic drift that increased the prevalence of some rare factor deficiencies. This comparatively high prevalence provides a potential pool of patients for genotype/phenotype research.