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目的了解反复孕育严重先天性心脏病儿、胎儿父亲患有原发性甲状旁腺功能低下家系的基因组拷贝数变化,确定其发病的遗传学原因。方法对常规染色体核型分析未见异常的法洛氏四联症胎儿及其整个家系中的7人采用微阵列基因组杂交(array-based comparative genomic hybridization,array-CGH)技术进行基因组拷贝数变化的检测分析(copy number variations,CNVs)。结果经过array-CGH分析,在胎儿及其父亲的22q11.21均发现存在2.52Mb的致病性缺失片段,位于18,919,942-21,440,514区段。家系中其他成员未发现同样的片段异常。结论 22q11.21微缺失是导致其父亲患原发性甲状旁腺功能减退的遗传学原因,也是该家系多次孕育严重先天性心脏病患儿的原因,同时表明22q11.21微缺失表型多样,临床症状差异大。array-CGH是一种高通量、高分辨率及高准确性的遗传学分析技术,能够发现染色体片段上的亚微结构异常,是临床遗传学研究的重要工具。
Objective To understand the genomic copy number changes of the children with severe congenital heart disease and fetal father who suffered from recurrent hypothyroidism and to determine the genetic causes of the disease. Methods Seven pairs of fetuses of Tetralogy of -fertility and their entire pedigrees with no abnormalities in conventional karyotype analysis were genotyped by array-based comparative genomic hybridization (array-CGH) Copy number variations (CNVs). Results After array-CGH analysis, a 2.52 Mb pathogenicity deletion fragment was found in the fetus and its father’s 22q11.21, located in the 18,919,942-21,440,514 region. Other members of the family did not find the same fragment abnormalities. Conclusion The microdeletion of 22q11.21 is the genetic cause of his father’s primary hypoparathyroidism and the reason why this pedigree has repeatedly conceived children with severe congenital heart disease and at the same time shows that the phenotype of 22q11.21 microdeletion is diverse The clinical symptoms vary greatly. Array-CGH is a high-throughput, high-resolution and high-accuracy genetic analysis technique that can detect sub-microstructural abnormalities on chromosome segments and is an important tool in clinical genetics.