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

ABSTRACT

BACKGROUND AND AIMS: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.