携带16号染色体单亲二倍体合并ORC6基因新突变的Meier—Gorlin综合征一例  

A boy with Meier-Gorlin syndrome carrying a novel ORC6 mutation and uniparental disomy of chromosome 16

作　　者：李娟[1] 丁宇[1] 常国营[1] 程青[1] 李辛[1] 王剑[2] 王秀敏[1] 沈亦平[2] 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心内分泌代谢科、医学遗传科,200127 [2]上海交通大学医学院附属上海儿童医学中心分子诊断实验室,200127

出　　处：《中华医学遗传学杂志》2017年第1期68-72,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81370930,81201353,81472051）

摘　　要：目的探讨1例因“生长发育迟缓伴小耳畸形”就诊的11岁男童的病因及临床特点。方法收集患儿的临床资料并进行生化检测、染色体芯片分析（chromosomal microarray analysis，CMA）、下一代基因测序以及Sanger测序。结果患儿存在宫内发育迟缓、出生后持续生长迟缓、小耳畸形、髌骨发育不良三联征以及特殊面容和正常促性腺激素性发育不良（小睾丸）。基因检测发现其16号染色体为单亲二倍体且存在ORC6基因c．67A〉G（P．Lys23Glu）纯合新突变。结论患儿可能为中国首例男童16号染色体为单亲二倍体合并ORC6基因纯合新突变导致的Meier-Gorlin综合征，该ORC6基因新突变经Alamut功能软件预测可能影响蛋白结构域功能。Objective To identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome （MGS）. Methods Chromosomal microarray analysis （CMA） was used to detect potential variations, while whole exome sequencing （WES） was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants. Results The boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normai gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c. 67A〉G （p. Lys23Glu） in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein. Conclusion The patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

关 键 词：Meier-Gorlin综合征 身材矮小 小耳畸形 原点识别复合物 单亲二倍体 

分 类 号：R440[医药卫生—诊断学] R725.9[医药卫生—临床医学]