Li Hening, Gong Yanfei, Chen Jingyi, Xie Liyun, Li Bojie, Xiang Yanghai, Xie Meihua
Yueyang Central Hospital, Yueyang, Hunan Province 414000, People's Republic of China.
J Genet. 2023;102.
The objective of the study was to perform the prenatal diagnosis of two foetuses with 22q11.2 duplication for 2.5 Mb after noninvasive prenatal testing (NIPT), and to explore the prenatal diagnosis and genetic characteristics of these foetuses. After amniocentesis, each foetus was diagnosed through karyotype analysis and single-nucleotide polymorphism array (SNP-array), and copy number variation using shotgun sequencing (CNV-seq) was carried out on each mother's peripheral blood for comparative analysis. Both pregnant woman 1 and pregnant woman 2 had foetal amniotic fluid chromosomal karyotypes of 46, XN. The SNP-array result for foetus 1 was arr[hg19] 22q11.21(18,648,856-21,800,471) x3; namely, 22q11.2 had a 3.1 Mb repeat, and the SNP-array result of foetus 2 was arr[hg19]22q11.2(18,648,855-21,464,764) x3; there was a 2.4 Mb repeat of 22q11.2. The CNV-Seq result of the peripheral blood of pregnant woman 1 was seq[hg19]22q11.2(18,953,139-21,449,967) x3; namely, in this mother's 22q11.2 region, there was ~2.5 Mb of duplicate fragment that was pathogenic to CNV. We confirmed that case 1 was inherited from the mother by CNV-seq. In both cases, however, there were key region deletions, including 41 OMIM genes such as , and . Both SNP-array and CNV-seq can effectively diagnose 22q11.2 duplication syndrome and clarify its fracture site and involved genes, which may facilitate understanding of the genotype and phenotype correlations.
本研究的目的是在无创产前检测（NIPT）后对两个22q11.2区域存在2.5 Mb重复的胎儿进行产前诊断，并探索这些胎儿的产前诊断及遗传特征。羊膜腔穿刺术后，通过核型分析和单核苷酸多态性阵列（SNP-array）对每个胎儿进行诊断，并对每位母亲的外周血进行鸟枪法测序拷贝数变异分析（CNV-seq）以进行对比分析。孕妇1和孕妇2的胎儿羊水染色体核型均为46,XN。胎儿1的SNP-array结果为arr[hg19] 22q11.21(18,648,856 - 21,800,471) x3；即22q11.2有3.1 Mb重复，胎儿2的SNP-array结果为arr[hg19]22q11.2(18,648,855 - 21,464,764) x3；22q11.2有2.4 Mb重复。孕妇1外周血的CNV-Seq结果为seq[hg19]22q11.2(18,953,139 - 21,449,967) x3；即在该母亲的22q11.2区域存在约2.5 Mb的重复片段，该片段对CNV具有致病性。通过CNV-seq我们证实病例1是由母亲遗传而来。然而，在这两个病例中均存在关键区域缺失，包括41个OMIM基因，如 、 和 。SNP-array和CNV-seq均可有效诊断22q11.2重复综合征，并明确其断裂位点及相关基因，这可能有助于理解基因型与表型的相关性。
