Two novel 1alpha-hydroxylase mutations in French-Canadians with vitamin D dependency rickets type I1

Kidney Int. 1998 Nov;54(5):1437-43. doi: 10.1046/j.1523-1755.1998.00133.x.


Background: Vitamin D dependency rickets type I (VDDR-I) is an autosomal recessive disorder in which 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-hydroxylase) activity in renal proximal tubules is deficient. VDDR-I is recognized throughout the world, but occurs more frequently in a subset of the French-Canadian population. We and others have recently cloned the human 1alpha-hydroxylase cDNA and gene, making it possible to screen for mutations. The first VDDR-I mutations were reported in one American and four Japanese patients. In this study, we screened for 1alpha-hydroxylase mutations in French-Canadian patients with VDDR-I.

Methods: The nine exons of the 1alpha-hydroxylase gene were amplified by polymerase chain reaction (PCR) from genomic DNA of four unrelated French-Canadian patients with VDDR-I and their parents, and sequenced.

Results: Three of the patients were homozygous for a single base-pair deletion (G) at position 262 in the cDNA that lies in exon 2, and causes a premature termination codon upstream from the putative ferredoxin- and heme-binding domains. The fourth patient was homozygous for a 7-bp insertion (CCCCCCA) at position 1323 of the cDNA that lies in exon 8, and causes a premature termination upstream from the putative heme-binding domain. In each family, obligate carriers have one copy of the mutant allele. These mutations, which could be detected by PCR-restriction fragment length polymorphism and polyacrylamide gel electrophoresis of the PCR products, were not found in 25 normal French-Canadians.

Conclusion: We describe two novel 1alpha-hydroxylase mutations that are consistent with loss of function in four French-Canadian patients with VDDR-I and suggest that the 1alpha-hydroxylase mutations arise from more than one founder in this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • Chromosome Mapping
  • Humans
  • Mutation*
  • Polymorphism, Restriction Fragment Length
  • Rickets / genetics*


  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase