Cassidy S B, Lai L W, Erickson R P, Magnuson L, Thomas E, Gendron R, Herrmann J
Section of Genetics/Dysmorphology, University of Arizona College of Medicine, Tucson 85724.
Am J Hum Genet. 1992 Oct;51(4):701-8.
Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). We describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor.
单亲二体最近被认为可导致人类疾病，包括普拉德-威利综合征（PWS）。我们描述了一个特别有启发性的病例，该病例提出了有关产生单亲二体机制的重要问题，并且对其评估提供了证据表明在胎儿中三体可能先于单亲二体出现。因孕妇年龄较大而进行的绒毛取样显示，所有直接检测的细胞和培养细胞中均存在15号染色体三体，尽管胎儿看起来正常。在15周时获取的羊水细胞进行的染色体分析，在研究的100多个细胞中均正常。该患儿出生时肌张力低下，高分辨率显带未能发现15q11 - 13缺失，而在50% - 70%的PWS患者中可发现该缺失。随着时间推移，PWS的典型特征逐渐显现。使用15号染色体探针进行的分子遗传学分析显示为母源单亲二体。在这个PWS病例中，母源染色体不分离，一个二体卵子由正常精子受精，随后父源15号染色体丢失，可能是导致局限性胎盘嵌合体和单亲二体的原因，而孕妇年龄较大可能是一个易感因素。
