title: Novel mutations of CYP27B1 gene lead to reduced activity of 1α-hydroxylase in Chinese patients.
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.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, China.
authors.forename: Ningyi
authors.initials: N
authors.lastname: Cui
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.forename: Yue
authors.initials: Y
authors.lastname: Chi
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.forename: Huaicheng
authors.initials: H
authors.lastname: Liu
authors.forename: Xunwu
authors.initials: X
authors.lastname: Meng
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhou
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D011859:Radiography; D012279:Rickets / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics; D014808:Vitamin D Deficiency / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase