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

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 normal 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.