1. Novel mutations of CYP27B1 gene lead to reduced activity of 1α-hydroxylase in Chinese patients.
- Author
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Cui N, Xia W, Su H, Pang L, Jiang Y, Sun Y, Nie M, Xing X, Li M, Wang O, Yuan T, Chi Y, Hu Y, Liu H, Meng X, and Zhou X
- Subjects
- Adolescent, Adult, Base Sequence, Blotting, Western, Child, Child, Preschool, China, DNA Mutational Analysis, Female, Humans, Male, Molecular Sequence Data, Mutant Proteins genetics, Mutant Proteins metabolism, Mutation, Missense genetics, Pedigree, Radiography, Rickets diagnostic imaging, Rickets enzymology, Rickets genetics, Vitamin D Deficiency diagnostic imaging, Vitamin D Deficiency enzymology, Vitamin D Deficiency genetics, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase genetics, Asian People genetics, Mutation genetics
- 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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