维生素D依赖性佝偻病ⅠA型2家系临床及分子遗传学分析  

Clinical and genetic analysis of vitamin D-dependent rickets type-1A in two Chinese families

作　　者：张继要[1] 孔惠敏[1] 周桃珍[2] 田培超[1] 董伟[1] 闫文浩 华爽 李振彪[1] 罗强 ZHANG Jiyao;KONG Huimin;ZHOU Taozhen;TIAN Peichao;DONG Wei;YAN Wenhao;HUA Shuang;LI Zhenbiao;LUO Qiang(Department of Pediatrics,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Prenatal Diagnostic Center,the Third Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院儿科,郑州450052 [2]郑州大学第三附属医院产前诊断中心,郑州450052

出　　处：《郑州大学学报（医学版）》2021年第6期883-888,共6页Journal of Zhengzhou University(Medical Sciences)

摘　　要：目的:分析2家系3例维生素D依赖性佝偻病(VDDR)-1A型患儿的临床特征及CYP27B1基因突变情况。方法:收集2个家系VDDR-1A 3例VDDR-1A患儿的临床表现、实验室检查和影像学资料。采集先证者及其他家系成员外周血标本,进行高通量测序,对CYP27B1基因异常检测并进行Sanger测序验证。结果与结论:家系1先证者为男性,家系2先证者及受累者为女性,早期均出现典型佝偻病体征、实验室及影像学检查改变。患儿对骨化三醇、钙剂治疗反应良好。家系1先证者c.844 C>T(p.Q282*)携带新发纯合无义突变,家系2先证者及其妹妹携带c.1358 G>A(p.R453H)、c.1357 C>T(p.R453C)复合杂合突变上述突变,可能是其患病原因。Aim:To analyze and summarize the clinical features of vitamin D dependent rickets type-1A(VDDR-1A)and CYP27B1 gene mutations among the three patients from two families in China.Methods:The clinical manifestations,laboratory examinations and radiographic data of the 3 patients with VDDR-1A from two families were collected,the blood samples of all the members of the 2 families were collected,then the hight-throughput sequencing of genes associated with hereditary bone diseases was performed.Sanger sequencing was used to determine the distribution of the abnormal sequences of CYP27B1 gene among the 2 families.Results and Conclusion:The propositus of lineage 1 was male,the propositus of lineage 2 and the other involved were female.All the patients presented typical signs,abnormal laboratory and imaging changesof rickets in early infancy.The affected ones responded well to calcitriol and calcium.CYP27B1 gene sequencing revealed de novo homozygous nonsense mutation of c.844 C>T(p.Q282*)in the propositus of lineage 1,and compound heterozygous mutations of c.1358 G>A(p.R453H)and c.1357 C>T(p.R453C)in the propositus and her sister of lineage 2,which may be the reason of the disease.

关 键 词：维生素D依赖性佝偻病1A型 1 25-二羟维生素D3 CYP27B1 

分 类 号：R725.8[医药卫生—儿科]