Two novel CYP2R1 mutations in a family with vitamin D-dependent rickets type 1b.

purposeVitamin D-dependent rickets type 1b (VDDR1b) is a very rare autosomal recessive disorder caused by mutations in CYP2R1 that produces 25-hydroxylase. To date only five mutations in CYP2R1 have been identified. This study has reported the genetic results and the clinical characteristics of a family with VDDR1b and compared this family to the other families with VDDR1b in literature.

methodsAfter two probands were diagnosed with VDDR1b, all other family members were evaluated. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25-hydroxy vitamin D, and 1.25-dihydroxy vitamin D levels were measured in all family members. All individuals were evaluated radiographically, and a genetic analysis was done in all family members. The other families with VDDR1b in literature were reviewed.

resultsTwo novel mutations [c.367 + 1G > C and p.E339Q (c.1015G > C)] were identified. The clinic and laboratory findings were strikingly different among the members of this family regardless of the mutation and the number of alleles affected. The families having different mutations in literature had also extensive variation in both the clinical and the laboratory findings.

conclusionThe current study further expands CYP2R1 mutation spectrum. The findings of both the current and the previous studies suggest that VDDR1b is a more complex disorder than the known autosomal recessive inheritance model and the phenotype may show an extensive variation regardless of the mutation type and the gene dosage.