Abstract：
Genomic disorders result from heterozygous copy number variants (CNVs). Homozygous deletions spanning numerous genes are rare, despite the potential contribution of consanguinity to such instances. CNVs in the 22q11.2 region are mediated by nonallelic homologous recombination between pairs of low copy repeats (LCRs), from amongst eight LCRs designated A-H. Heterozygous distal type II deletions (LCR-E to LCR-F) have incomplete penetrance and variable expressivity, and can lead to neurodevelopmental issues, minor craniofacial anomalies, and congenital abnormalities. We report siblings with global developmental delay, hypotonia, minor craniofacial anomalies, ocular abnormalities, and minor skeletal issues, in whom chromosomal microarray identified a homozygous distal type II deletion. The deletion was brought to homozygosity as a result of a consanguineous marriage between two heterozygous carriers of the deletion. The phenotype of the children was strikingly more severe and complex than that of the parents. This report suggests that the distal type II deletion harbors a dosage-sensitive gene or regulatory element, which leads to a more severe phenotype when deleted on both chromosomes.
摘要：
基因组病症由杂合拷贝数变异体(CNV)引起。跨越许多基因的纯合缺失很少见，尽管血缘关系对这种情况有潜在的贡献。22q11.2区域中的CNV是由低拷贝重复序列（LCR）对之间的非等位基因同源重组介导的，来自指定为A-H的八个LCR。杂合远端II型缺失（LCR-E至LCR-F）具有不完全的外显率和可变的表达率，并可能导致神经发育问题，轻微的颅面异常,和先天性异常。我们报告了全球发育迟缓的兄弟姐妹，低张力,轻微的颅面异常,眼部异常，和轻微的骨骼问题，其中染色体微阵列鉴定出纯合远端II型缺失。由于缺失的两个杂合携带者之间的亲缘婚姻，使缺失达到纯合性。儿童的表型比父母的表型明显更严重和复杂。该报告表明，远端II型缺失具有剂量敏感基因或调节元件，当两条染色体上缺失时，会导致更严重的表型。
