摘要
目的探讨单核苷酸多态性微阵列芯片（single nucleotide polymorphism array, SNP-array）在生长迟缓患儿遗传学检查中的应用价值。方法对181例生长迟缓的患儿，采用Illumina Human Cyto SNP-12微阵列芯片进行全基因组拷贝数变异（copy number variations，CNVs）检测，结合查询国际病理性CNVs数据库（ClinGen、ClinVar、DECIPHER、OMIM）、正常人基因组变异数据库（Database of Genomic Variants, DGV）以及PubMed文献数据库等对检出的CNVs的致病性进行分析。结果共检出47例变异阳性患儿，检出率约26％，其中包括已知的微缺失／重复综合征12例（占26％）、明确致病的CNVs（非综合征）10例（21％）、染色体数目异常3例（6％）、染色体非平衡易位3例（6％）、致病性嵌合4例（9％）、临床意义不明的CNVs15例（32％）。剔除染色体水平明显可见的数目与结构异常后，共检出15例小于5Mb的明确致病性CNVs，这是常规染色体核型分析所无法检出的。此外，还检出3例包含已知或预测为印迹基因的杂合性丢失（loss of heterozygosity,LOH）患儿以及2例亲本可能存在血缘关系的患儿。结论SNP-array技术具有分辨率高、准确性好等优点，是生长迟缓患儿遗传学诊断的有力工具。
Objective To explore the value of single nucleotide polymorphism array （SNP-array） for the analysis of pediatric patients with growth retardation. Methods One hundred eighty one children with growth retardation were enrolled. DNA was extracted from peripheral samples from the patients, and whole genome copy number variations （CNVs） were detected using Illumina Human Cyto SNP-12. All identified CNVs were further analyzed with reference to databases including ClinGen, ClinVar, DECIPHER, OMIM and DGV as well as comprehensive review of literature from PubMed to determine their pathogenicity. Results Forty seven patients （26%） with abnormal CNVs were detected, which included 12 known microdeletions/microduplications syndrome （ 26%）, 10 pathogenic non-syndromic CNVs （ 21%）, 3 numerical chromosome aberrations （6M）, 3 unbalanced translocations （6M）, 4 pathogenic mosaicisms （9~） and 15 cases with unknown clinical significance （32~）. After excluding obvious numerical and/or structural chromosomal abnormalities, this study has detected 15 pathogenic microdeletions/ microduplications sized 5 Mb or less, which may be missed by routine chromosomal karyotyping. In addition, there were 3 cases with loss of heterozygoisty （LOH） containing known or predicted imprinting genes as well as 2 cases with suspected parental consanguinity. Conclusion SNP-array technology is a powerful tool for the genetic diagnosis of children with growth disorders with advantages of high resolution and improved accuracy.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2017年第3期321-326,共6页
Chinese Journal of Medical Genetics
基金
国家科技基础性工作专项课题（SQ2014FY3600002）
广西医药卫生自筹课题（Z2015238）
关键词
生长迟缓
拷贝数变异
微缺失/重复
单核苷酸多态性微阵列芯片
Growth retardation
Copy number variation
Microdeletion/Microduplication
Single nucleotide polymorphism-array
