Schimke免疫-骨发育不良儿童基因分析  

SMARCAL1 gene analysis of 2 Chinese Schimke immuno-osseous dysplasia children

作　　者：王薇[1] 宋红梅[1] 魏珉[1] 邱正庆[1] 王晨[1] 张玉[1] 李明[1] 袁裕衡 唐晓艳[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院儿科,100730

出　　处：《中华儿科杂志》2015年第1期45-50,共6页Chinese Journal of Pediatrics

基　　金：基金项目：2014年度公益性行业科研专项（201402012）

摘　　要：目的对2例临床疑似Schimke免疫-骨发育不良（Schimke immuno-osseous dysplasia，SIOD）患儿进行SMARCAL1基因分析，寻找致病突变，进而了解中国人SMARCAL1基因突变类型以及基因诊断的意义。方法对2008-2014年于北京协和医院就诊的2例临床表现为脊柱骨骺发育不良、身材矮小不对称，进行性加重的肾病综合征，细胞免疫功能缺陷的疑似SIOD患儿，在获得知情同意后，取患儿及其父母新鲜抗凝外周血，常规提取DNA，设计引物后对SMARCAL1全部16个外显子及外显子内含子交界处进行PCR扩增，经凝胶电泳分离PCR产物，纯化，测序。并对发现的错义变异进行SIFT软件验证以及50名正常人测序验证。结果（1）2例患儿共检测到4种基因变异：两种错义变异：c．1129G〉C，P．Glu377Gln及c．1933C〉T，P．Arg645Cys。两种剪切突变：c．1334＋1G〉A及c．2142．1G〉A。（2）c．1129G〉C，P．G1u377Gln为已报道的致病突变，检验50名正常人中，15名携带此变异，证实其为单核苷酸多态性，而非致病突变。（3）c．1334＋1G〉A及c．2142．1G〉A为本研究发现的两种新突变。结论（1）通过SMARCALl基因分析，共检测到3种致病突变，发现新突变2种。（2）错义变异c．1129G〉C，p．Glu377Gln至少在中国人种中为单核苷酸多态性，而非致病突变。Objective Schimke immuno-osseous dysplasia （SIOD）, is an autosomal recessive inherited disease caused by SMARCAL1 （MIM ：20606622） mutations,while in about half of the patients no any mutation in SMARCAL1 could be found. This disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections, and hyperpigmented macules. This study aimed to analyze SMARCAL1 gene of 2 unrelated suspected SIOD children, to make definite diagnosis, and find more SMARCAL1 mutation types of Chinese SIOD. Method Two suspected Chinese HaM male SIOD children who visited our hospital from 2008 to 2014, aged 3 y 6 m and 7 y 8 m, both were short and had spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections. After informed consent, they and their parents＇s DNA were extracted from blood. PCRs for all 16 exons of SMARCAL1 were performed and PCR products were purified by 2% gel electrophoresis and sequenced directly. Pathogenicity of missense variations was confirmed by SIFT and sequencing SMARCAL1 of fifty normal controls. Result （ 1 ） Four gene variations were found in the two children： Two reported missense mutations c. 1129G 〉 C, p. Glu377Gln and c. 1933C 〉 T, p. Arg645Cys. Two splicing mutations c. 1334 ＋ 1G 〉 A and c. 2142-1 G 〉 A were detected. （2） c. 1129G 〉C, p. Glu377Gln were reported as a disease-causing mutations before, but it was an single nucleotide polymorphism （SNP） which was found in 15 of 50 normal controls. （3）Two novel splicing mutations were found in this study： c. 1334 ＋ 1G 〉 A and c. 2142-1 G 〉 A. Conclusion （ 1 ） We detected 3 diseasecausing mutations in 2 SIOD children by SMARCAL1 gene analysis, while 2 splicing mutations were novel mutations. （2） c. 1129G 〉 C, p. Glu377Gln was a SNP but not a disease-causing mutation at least in Chinese population.

关 键 词：Schimke免疫-骨发育不良 SMARCAL1 突变 单核苷酸多态性 中国 

分 类 号：R726.8[医药卫生—儿科]