拷贝数变异分析及染色体核型分析在发育迟缓与智力障碍儿童中的应用

Application of copy number variation analysis and chromosome karyotype analysis in children with developmental delay/intellectual disability

目的探讨拷贝数变异分析及染色体核型分析在发育迟缓/智力障碍(DD/ID)儿童中的应用。方法对湖南省儿童医院连续649例DD/ID患儿进行染色体微阵列(CMA)检测。通过参考以前的报告或使用荧光原位杂交(FISH)及定量聚合酶链反应(q-PCR)进行的亲本检测结果来评估拷贝数变异(CNV)的致病性。结果649例DD/ID患儿中有110例检出致病性CNV,检出率为16.9%,其中包括长度为270 kb~30 Mb的100个缺失和31个重复。对66例患儿父母进行CMA检测,其中86.4%携带新生CNV。8例患儿的致病性CNV遗传自健康父母,具有平衡易位。在2p21p16.3、3p21.31、10p11.22、14q24.2和21q22.13位点验证了5个罕见报告的缺失。结论CMA检测在DD/ID患儿的基因诊断中具有临床实用性。CMA检测可作为所有DD/ID儿童的临床诊断检测。

Objective To investigate the application of copy number variation analysis and chromosome karyotype analysis in children with developmental delay/intellectual disability(DD/ID).Methods Chromosome microarray(CMA)detection was performed in 649 consecutive children with DD/ID in Hunan Children's Hospital.Medical records were reviewed retrospectively.Pathogenicity of detected copy number variations(CNV)was evaluated by referencing previous reports or parental testing using fluorescence in situ hybridization(FISH)and quantitative polymerase chain reaction(q-PCR).Results In 649 children with DD/ID,110 cases were found with pathogenic CNV,and the diagnostic yield was 16.9%,including 100 deletions and 31 duplications of 270 kb-30 Mb.Parental testing was performed in 66 patients,86.4%of which carried de novo CNVs.In eight children,pathogenic CNVs were inherited from healthy parents with a balanced translocation,and genetic counseling was provided to these families.Five rarely reported deletions were verified on 2p21p16.3,3p21.31,10p11.22,14q24.2 and 21q22.13 sites.Conclusions CMA test has clinical practicability in genetic diagnosis of patients with DD/ID.CMA test should be used as a clinical diagnostic test for all children with DD/ID.