Genetic and clinical characteristics of the patients with Vitamin D Dependent Rickets Type 1A.

Objective: Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in the 1 alpha-hydroxylase gene (CYB27B1). As it may be confused with nutritional rickets and hypophosphatemic rickets, genetic analysis is important for making a correct diagnosis. Methods: We analysed genomic DNA from II patients from eight different Turkish families. The patients were recruited for our studies if they presented with a diagnosis of VDDR. Results: The mean +/- standard deviation age at diagnosis was 13.1 +/- 7.4 months. Seven patients had mild hypocalcemia at presentation while four patients had normal calcium concentrations. All patients underwent CYP27B1 gene analysis. The most prevalent mutation was the c.195 + 2T > G splice donor site mutation, affecting five out of II patients with VDDR1A. Two patients from the fourth family were compound heterozygous for c. 195 + 2T > G and c.195 + 2 T > A in intron-1. Two patients, from different families, were homozygous for a previously reported duplication mutation in exon 8 (1319_1 325dupCCCACCC, Phe443Profs*24). One patient had a homozygous splice site mutation in intron 7 (c. 1215 + 2 T > A) and one patient had a homozygous mutation in exon 9 (c.1474 C > T). Conclusion: Intron-1 mutation was the most common mutation, as previously reported. All patients carrying that mutation were from same city of origin suggesting a "founder" or a "common ancestor" effect. VDDR 1 A should definitely be considered when a patient with signs of rickets has a normal 25-OHD level or when there is unresponsiveness to vitamin D treatment.