AI Article Synopsis
- Pseudovitamin D-deficiency rickets (PDDR) is a genetic disorder caused by mutations in the 1α-hydroxylase enzyme, which is essential for vitamin D metabolism.
- Ten mutations in the CYP27B1 gene were identified across eight Chinese families, including six novel missense mutations and three novel deletion mutations.
- Functional tests showed that these missense mutations retain only about 5.5-12.1% of the normal enzyme activity, linking these genetic changes to the disease's symptoms.
Article Abstract
Pseudovitamin D-deficiency rickets (PDDR) is an autosomal recessive disorder resulting from a defect in renal 25-hydroxyvitamin D 1α-hydroxylase, the key enzyme in the pathway of vitamin D metabolism. We identified ten different mutations in the 1α-hydroxylase gene (CYP27B1) in eight Chinese families with PDDR by DNA-sequence analysis. Six of them are novel missense mutations: G57V, G73W, L333F, R432C, R459C, and R492W; three are novel deletion mutations: c48-60del, c1310delG, and c1446delA; and an insertion mutation c1325-1332insCCCACCC reported previously. Functional assay revealed that the missense mutants identified in this study retain 5.5-12.1% 1α-hydroxylase activity of the wild type. The study describes nine novel mutations in addition to 37 known mutations of CYP27B1 gene and shows the correlation between these mutations and the clinical findings of 1α-hydroxylase deficiency.
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