Table1_Case report: Molecular analysis of a 47,XY,+21/46,XX chimera using SNP microarray and review of literature.DOCX

Chimerism is a very rare genetic finding in human. Most reported cases have a chi 46,XX/46,XY karyotype. Only three non-twin cases carrying both trisomy 21 and a normal karyotype have been reported, including two cases with a chi 47,XY,+21/46,XX karyotype and a case with a chi 47,XX,+21/46,XY karyotype. Herein we describe an additional case with a chi 47,XY,+21/46,XX karyotype. For the case, a physical examination at the age of 1 year revealed ambiguous genitalia with no features of Down syndrome or other malformations. Growth and developmental milestones were within normal ranges. We performed short tandem repeat (STR) and single nucleotide polymorphism (SNP) microarray analyses to attempt to identify the mechanism underlying the chimerism in this patient and the origin of the extra chromosome 21. Cytogenetic analyses of the patient’s peripheral blood revealed approximately 17% of a 47,XY,+21 lineage by G-banding karyotype analysis, 13%–17% by FISH analyses of uncultured peripheral blood, and 10%–15% by SNP microarray analysis. Four years later, the percentage of trisomy 21 cells had decreased to approximately 6%. SNP microarray and STR analyses revealed a single maternal and double paternal genetic contribution to the patient for the majority of the markers, including the chromosome 21 markers. The extra chromosome 21 was paternally derived and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanisms underlying chimera in our case was likely fertilization two spermatozoa, one with an ovum and the other with the second polar body.

嵌合体（Chimerism）是人类中极为罕见的遗传学异常。目前已报道的病例多数为46,XX/46,XY核型嵌合体。迄今仅报道过3例非双胎的同时携带21三体与正常核型的嵌合体病例，其中2例为47,XY,+21/46,XX核型嵌合体，1例为47,XX,+21/46,XY核型嵌合体。本文新增报道1例47,XY,+21/46,XX核型嵌合体病例。该患者1岁时的体格检查显示外生殖器性别不清，无唐氏综合征（Down syndrome）或其他畸形特征，其生长发育里程碑均处于正常范围内。我们通过短串联重复序列（STR）与单核苷酸多态性（SNP）微阵列分析，尝试明确该患者嵌合体的发生机制以及额外21号染色体的起源。对患者外周血的细胞遗传学分析显示：G显带核型分析检出约17%的47,XY,+21细胞群；未培养外周血的荧光原位杂交（FISH）分析检出13%~17%的异常细胞；SNP微阵列分析检出10%~15%的异常细胞。四年后，21三体细胞的比例降至约6%。SNP微阵列与STR分析显示，该患者多数遗传标记（包括21号染色体标记）均呈现单一母源、双父源的遗传贡献模式。额外的21号染色体源自父方，提示减数分裂I期不分离可能发生于精子发生过程中。本病例的嵌合体发生机制大概率为两枚精子分别与卵细胞及第二极体完成受精。