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 25OHD 1α-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 11 patients from 8 different Turkish families. The patients were recruited for our studies if they presented with diagnosis of vitamin D dependent rickets.

RESULTS: The mean age at diagnosis was 13.1 ±7.4 months. Seven patients had mild hypocalcemia at presentation while 4 patients had normal calcium levels. All patients underwent CYP27B1 gene analysis; The most prevalent mutation was the c.195 + 2T>G splice donor site mutation, affecting 5 out of 11 patients with VDDR1A. Two patients from the fourth family was 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_1325dupCCCACCC, Phe443Profs*24). One patient had homozygous splice site mutation in intron 7 (c.1215+2 T>A). And one patient had homozygous mutation in exon 9 (c.1474 C>T).

CONCLUSION: Intron 1 mutation was the most common mutation as in the previous studies, and all patients carrying that mutation were from same city of origin suggesting a "founder" or a "common ancestor" effect. VDDR1A should be definitely considered when a patient with signs of rickets has a normal 25-OH level or when there is unresponsiveness to vitamin D treatment.