染色体微阵列分析技术在210例发育迟缓/智力低下患儿中的应用

Application of chromosomal microarray analysis in 210 children with developnental delay/intellectual disability

目的探讨染色体微阵列分析技术(CMA)在检查核型分析未见异常的发育迟缓/智力低下(DD/ID)患儿方面的应用价值。方法选取210例DD/ID伴或不伴其他异常患儿,分为2组:单纯性DD/ID组( n =90),复杂性DD/ID组( n =120例,合并癫痫23例、头颅磁共振异常36例、心血管系统19例、多发结构畸形42例)。提取其外周血DNA,采用CGXv1.18-plex基因芯片进行全基因组拷贝数变异(CNVs)检测,查询国际病理性CNV数据库(ClinVar、DECIPHER、OMIM等)、DGV数据库,检索PubMed数据库相关文献,对CNVs致病性进行分析。结果在210例DD/ID患儿中检出83例染色体拷贝数异常,检出率为39.5%。其中,检出已知致病的常见微缺失/微重复综合征66例;罕见综合征1例(Kleefstra综合征)。可疑致病变异的微缺失/微重复9例,可能良性变异1例,临床意义不明6例。结论 CMA可以明显提高DD/ID患儿遗传学病因的诊断率,对于患儿的治疗及其父母的再生育具有重要的指导意义。因此可以作为DD/ID患儿的一线诊断方法。

Objective To access the value of chromosome microarray analysis (CMA) for identifying the children of developmental delay/intellectual disability(DD/ID)without karyotype abnormalities. Methods 210 children of developmental delay/intellectual disability(DD/ID) were selected and divided into 5 groups: children were classified as with isolated DD/ID group( n =90),DD/ID with epilepsy group( n =23),DD/ID with skull mri abnormality group( n =36),DD/ID with disease of cardiovascular system group( n =19),DD/ID with other structural malformations( n =42).Genome DNA was extracted from peripheral blood and was analyzed with the whole genome copy number variation (CNVs) by cgxv1.18-plex gene chip.All identified copy number variants (CNVs) were analyze with references from databases such as ClinVar,DECIPHER,OMIM and Database of Genomic Variants(DGV),as well as comprehension literature review from PubMed database to determine the pathogenicity of CNVs. Results 83 cases(39.5%) in 210 children with DD/ID were detected chromosomal copy number abnormality,including 66 cases microdeletion /microduplications associated with known syndromes,1 case of rare syndrome (Kleefstra syndrome);3 cases microdeletion /microduplications associated with suspected pathogenic variation,1 case been benign variation,5 cases CNVs of unknown clinical significance. Conclusion CMA can significantly improve the diagnosis rate for patients with DD/ID,and it has important guiding significance for the treatment of children and the reproduction of their parents.Therefore,it can be used as a first-line diagnosis method for patients with DD/ID.