Population genetics of vitamin D-dependent rickets in northeastern Quebec.

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.