De Braekeleer M, Larochelle J
Department of Human Sciences, Université du Québec à Chicoutimi, Canada.
Ann Hum Genet. 1991 Oct;55(4):283-90. doi: 10.1111/j.1469-1809.1991.tb00855.x.
Vitamin D-dependent rickets (VDD1) is an autosomal recessive disorder that was recognized in Saguenay-Lac-St-Jean (SLSJ) in 1970. The great majority of the VDD1 cases reported in the French Canadian population of Quebec originated from SLSJ, Charlevoix, and the Haute Côte Nord, all regions located in northeastern Quebec. The prevalence at birth in SLSJ was estimated at 1/2916 live borns, and the carrier rate was estimated at 1/27 inhabitants in the SLSJ region. The mean coefficient of inbreeding was not elevated in the VDD1 group of SLSJ compared with three matched control groups. The mean coefficient of kinship was 2.5 times higher in the VDD1 group than in the control groups. In the SLSJ region, the places of origin of the VDD1 children and their children did not show a clustered non-uniform distribution. Endogamy was not found to be higher in the VDD1 group than in control groups. The genealogical reconstruction showed all the obligate carriers of the VDD1 gene, but one, to be related to a small set of founders who settled in New France in the 17th century. All these results, as well as a strong linkage disequilibrium between RFLPs located on the long arm of chromosome 12 and the VDD1 locus, support the hypothesis of a founder effect for VDD1. They also suggest that a unique mutation accounts for most, if not all, of the cases known in northeastern Quebec.
维生素D依赖性佝偻病（VDD1）是一种常染色体隐性疾病，于1970年在萨格奈-拉克圣让（SLSJ）地区被发现。在魁北克法裔加拿大人群中报告的绝大多数VDD1病例都来自SLSJ、沙勒沃伊和北高海岸地区，所有这些地区都位于魁北克东北部。据估计，SLSJ地区的出生患病率为1/2916活产儿，携带者率估计为SLSJ地区每27名居民中有1人。与三个匹配的对照组相比，SLSJ地区VDD1组的平均近亲繁殖系数并未升高。VDD1组的平均亲属系数比对照组高2.5倍。在SLSJ地区，VDD1患儿及其子女的出生地并未呈现出聚集性的非均匀分布。未发现VDD1组的族内通婚率高于对照组。系谱重建显示，除一人外，所有VDD1基因的必然携带者都与一小群17世纪定居在新法兰西的奠基者有关。所有这些结果，以及位于12号染色体长臂上的限制性片段长度多态性（RFLP）与VDD1基因座之间的强连锁不平衡，都支持VDD1存在奠基者效应的假说。它们还表明，一个独特的突变导致了魁北克东北部已知的大多数（如果不是全部）病例。
