A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
复制标题
维生素 D 依赖性 1A 型佝偻病中国家系中 CYP27B1 的新复合突变
DOI：
10.1515/jpem-2013-0183
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发表时间：
2014-03-01
影响因子：
1.4
通讯作者：
Zhang, Zhen-Lin
中科院分区：
文献类型：
--
作者：
Hu, Wei-Wei;Ke, Yao-Hua;Zhang, Zhen-Lin
目的：编码维生素D1a-羟基酶的细胞色素P27B1基因突变是维生素D依赖型1A型(VDDR1A型，MIM 264700)的遗传基础。本研究的目的是研究一种新的CYP27B1突变及其临床表现。方法：根据临床表现、体格检查、X线片上的骨骼特征和实验室结果诊断VDDR1A。结果：我们对一名5岁男童的CYP27B1基因进行了测序，该男童从12个月开始就表现为生长迟缓，并有频繁的手、腿和口周抽动的病史。我们发现了一个由两个错义突变组成的复合杂合突变：一个在外显子7(R389C[c.1165C>；T])，另一个在外显子8(R459C[c.1375C>；T])。我们以野生型CYP27B1为受体，钙二醇为配基，预测R459位点与钙二醇的相互作用。根据预测的结构，野生型R459残基位于CyP27B1与其配体结合的口袋上。结论：根据人类基因突变数据库，在本病例中发现的复合杂合性突变为新的杂合性突变，尚未见文献报道。该突变为VDDR1A的进一步研究和临床诊断学的发展提供了新的基础。
Objectives: Mutations in the CYP27B1 gene, which encodes vitamin D 1a-hydroxylase, are the genetic basis of vitamin D-dependent rickets type 1A (VDDR1A, MIM 264700). The aim of this study was to investigate a novel CYP27B1 mutation and its clinical manifestations.Methods: VDDR1A was diagnosed based on clinical presentation, a physical examination, bone characteristics on an X-ray, and laboratory results. A molecular model of the CYP27B1 protein was constructed using the SWISS-MODEL server and Swiss-PdbViewer.Results: We sequenced the CYP27B1 gene in a 5-year-old male child who presented with growth retardation and a history of frequent hand, leg, and perioral twitching since the age of 12 months. We identified a compound heterozygous mutation consisting of two missense mutations: one in exon 7 (R389C [c. 1165C > T]) and one in exon 8 (R459C [c. 1375C > T]). We used the wild-type CYP27B1 as a receptor and calcidiol as a ligand to predict the interaction between the R459 site and calcidiol. According to the predicted structure, the wild-type R459 residue localizes to the pocket where CYP27B1 binds to its ligand.Conclusions: According to the Human Gene Mutation Database, the compound heterozygous mutation identified in our patient is novel and has not yet been reported in the literature. This mutation provides a new basis for further research on VDDR1A and for the development of clinical diagnostics.