DeLozier-Blanchet C D, Roeder E, Denis-Arrue R, Blouin J L, Low J, Fisher J, Scharnhorst D, Curry C J
Division of Medical Genetics, Geneva University Hospital, Geneva, Switzerland.
Am J Med Genet. 2000 Dec 18;95(5):444-9. doi: 10.1002/1096-8628(20001218)95:5<444::aid-ajmg7>3.0.co;2-x.
This patient, in whom trisomy 12 mosaicism was confirmed in multiple organs, is the fifth case diagnosed postnatally and the first reported for whom a meiotic origin of the trisomy, maternal meiosis I, was determined. Mosaic aneuploidy was suspected because of pigmentary dysplasia, a frequent but non-specific finding in chromosomal mosaicism. The severe phenotype of this child, who died in infancy with a complex heart malformation, was probably a result of the high percentage of trisomic cells. Cytogenetic and interphase fluorescent in situ hybridization analyses showed a highly variable distribution of aneuploid cells in the nine tissues studied, from none in blood and ovary to 100% in spleen and liver. The trisomy arose meiotically with apparent post-zygotic loss of one of the chromosomes 12; uniparental disomy for this chromosome in the diploid cell line was excluded. The phenotype of the cases reported in living or liveborn individuals has been extremely variable, ranging from the present case, in which the child died in infancy with multiple malformations and pigmentary dysplasia, to a fortuitous finding in an adult studied for infertility. The variation in severity is probably determined by the proportion and distribution of the trisomic cells, which is linked to the timing of the non-disjunctional error.
该患者多个器官均确诊存在12号染色体三体嵌合体，是出生后确诊的第五例，也是首例报告确定三体源于减数分裂（母源性减数分裂I）的病例。因色素发育异常怀疑存在嵌合非整倍体，色素发育异常是染色体嵌合体中常见但非特异性的表现。该患儿因复杂心脏畸形于婴儿期死亡，其严重表型可能是三体细胞比例高所致。细胞遗传学和间期荧光原位杂交分析显示，在所研究的9个组织中，非整倍体细胞分布高度可变，血液和卵巢中无，脾脏和肝脏中达100%。三体源于减数分裂，12号染色体之一在合子后明显丢失；排除了二倍体细胞系中该染色体的单亲二体性。已报告的存活或活产个体病例的表型差异极大，从本例患儿因多种畸形和色素发育异常于婴儿期死亡，到因不育接受检查的成年人中的偶然发现。严重程度的差异可能由三体细胞的比例和分布决定，这与不分离错误发生的时间有关。
