Akademik Veri Yönetim Sistemi
CLINICAL ENDOCRINOLOGY, cilt.77, sa.3, ss.363-369, 2012 (SCI-Expanded)
Context Vitamin D-dependent rickets type 1A (VDDR-IA, OMIM 264700) is a rare autosomal recessive disorder and is caused by mutations in the CYP27B1 gene. Objectives We aim to investigate CYP27B1 mutation in seven patients from four separate families and characterize the genotypephenotype correlation. Methods The entire coding region of the CYP27B1 gene was sequenced, and genotypephenotype correlation among patients was assessed. Results Sequencing analysis identified biallelic CYP27B1 mutations in all patients and monoallelic mutations in their parents. One patient from the first family was compound heterozygous for c.1166G>A (p.Arg389His) and a novel nonsense mutation c.1079 C>A (p.Ser360*). Two patients from the second family were homozygous for a novel splice donor site mutation in intron 1 (c.195 similar to+similar to 2 T>G), causing partial retention of the intron and a shift in the reading frame. Both novel mutations lead to the complete loss of vitamin D1a-hydroxylase activity. Four patients from families 3 and 4 were homozygous for a previously reported duplication mutation in exon 8 (13191325dupCCCACCC, Phe443Profs*24). Interestingly, one patient who was presented with severe hypocalcaemia and seizures at 4 similar to months of age as a result of Phe443Profs*24 has improved spontaneously since 11 similar to years of age and does not need regular treatment. Her laboratory tests showed normal serum calcium and 1,25(OH)2D after refusing to take medication for 12 similar to months. Conclusions There is a good genotypephenotype correlation in VDDR-IA. However, some patients may recover from the loss of CYP27B1 function, probably due to 1a-hydroxylase activity exerted by a non-CYP27B1 enzyme.