Martin Megan M, Vanzo Rena J, Sdano Mallory R, Baxter Adrianne L, South Sarah T
Lineagen, Inc., Salt Lake City, Utah.
Department of Pediatrics and Pathology, University of Utah, Salt Lake City, Utah.
Am J Med Genet A. 2016 Jan;170A(1):243-8. doi: 10.1002/ajmg.a.37407. Epub 2015 Oct 5.
We report on a unique case of a mosaic 20pter-p13 deletion due to a somatic repair event identified by allele differentiating single nucleotide polymorphism (SNP) probes on chromosomal microarray. Small terminal deletions of 20p have been reported in a few individuals and appear to result in a variable phenotype. This patient was a 24-month-old female who presented with failure to thrive and speech delay. Chromosomal microarray analysis (CMA) performed on peripheral blood showed a 1.6 Mb deletion involving the terminus of 20p (20pter-20p13). This deletion appeared mosaic by CMA and this suspicion was confirmed by fluorescence in situ hybridization (FISH) analysis. Additionally, the deletion interval at 20p was directly adjacent to 15 Mb of mosaic copy-neutral loss of heterozygosity (LOH). The pattern of SNP probes was highly suggestive of a somatic repair event that resulted in rescue of the deleted region using the non-deleted homologue as a template. Structural mosaicism is rare and most often believed to be due to a postzygotic mechanism. This case demonstrates the additional utility of allele patterns to help distinguish mechanisms and in this case identified the possibility of either a post-zygotic repair of a germline deletion or a post-zygotic deletion with somatic recombination repair in a single step.
我们报告了一例因体细胞修复事件导致的独特的20pter-p13镶嵌性缺失病例，该事件通过染色体微阵列上的等位基因区分单核苷酸多态性（SNP）探针得以识别。少数个体中曾报道过20p的小末端缺失，其似乎会导致可变的表型。该患者为一名24个月大的女性，表现为生长发育迟缓及语言发育延迟。对外周血进行的染色体微阵列分析（CMA）显示存在一个1.6 Mb的缺失，累及20p的末端（20pter-20p13）。通过CMA，该缺失呈现镶嵌性，荧光原位杂交（FISH）分析证实了这一怀疑。此外，20p处的缺失区间紧邻15 Mb的镶嵌性杂合性拷贝中性缺失（LOH）。SNP探针的模式强烈提示了一个体细胞修复事件，该事件利用未缺失的同源物作为模板挽救了缺失区域。结构镶嵌现象罕见，通常认为是由于合子后机制所致。本病例展示了等位基因模式在帮助区分机制方面的额外作用，在该病例中确定了种系缺失的合子后修复或一步完成的体细胞重组修复导致合子后缺失这两种可能性。
