Novel vitamin D 1α-hydroxylase gene mutations in a Chinese vitamin-D-dependent rickets type I patient.

Hereditary rickets is classified into four types: X-linked hypophosphatemic vitamin-D-resistant rickets, autosomal dominant hypophosphatemic vitamin-D-resistant rickets, vitamin-D-dependent rickets type I, and vitamin-D-dependent rickets type II, and the genes responsible are PHEX, FGF23, CYP27B1 and VDR, respectively (Clausmeyer et al. 2009; Gribaa et al. 2010; Malloy et al. 2010). Vitamin-Ddependent rickets type I (VDDR-I, MIM 264700), also known as vitamin D 1α-hydroxylase deficiency or pseudovitamin D deficiency rickets, is a rare autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia. VDDR-I is caused by mutations of the 25hydroxyvitamin D 1α-hydroxylase gene (CYP27B1, MIM 609506) (Wang et al. 1998; Kitanaka et al. 1998). We identified compound heterozygous mutations in CYP27B1 gene in a Chinese VDDR-I patient. Both mutations are novel and include a small 11 nucleotide deletion (c.311321delGGCCCGAGCGC, p.R104LfsX225) in exon 2 that alters the downstream reading frame and creates a premature TGA stop signal at codon 328, and a missense mutation (c.473T>C, p.L158P) in exon 3 causing the amino acid change L158P. This study confirms the relationship between mutations of the CYP27B1 gene and the clinical findings of vitamin-D-dependent rickets type I.