Genotype and Phenotype Characteristics in 22 Patients with Vitamin D-Dependent Rickets Type I

Vitamin D-dependent rickets type I (VDDR1) is an autosomal recessive disorder caused by mutations in the 25-hydroxyvitamin D 1-alpha-hydroxylase gene (CYP27B1). Mutations in CYP27B1 disrupt or lead to a total loss of the 1-α-hydroxylase activity and require treatment with physiological doses of calcitriol.

A genetic analysis of the CYP27B1 gene was conducted in 22 Turkish patients with VDDR1 from 13 families. Presenting characteristics, biochemical features, treatment, and results from the genetic analysis are described.

A splice donor site mutation c.195 + 2T>G was found in 10 patients. The novel missense p.192K>E (c.574A>G) mutation was detected in 5 patients, and a novel missense p.197G>D (c.590G>A) mutation was found in 4 patients. A previously reported 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) in exon 8 was detected in 1 patient, and 1 patient was a compound heterozygote for the novel p.192K>E and the previously described 1319-1325dupCCCACCC mutations. A novel single base pair deletion, c.171_171delG, leading to a frameshift, was found in 1 patient.

We identified 3 novel and 2 previously described mutations in the CYP27B1 gene. A marked phenotypical diversity was observed between families that carried identical mutations, suggesting phenotypical heterogeneity.