Horsthemke B, Buiting K
Institut fur Humangenetik, Universitatsklinikum Essen, Essen, Germany.
Cytogenet Genome Res. 2006;113(1-4):292-9. doi: 10.1159/000090844.
The Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurogenetic diseases that are caused by the loss of function of imprinted genes on the proximal long arm of human chromosome 15. In a few percent of patients with PWS and AS, the disease is due to aberrant imprinting and gene silencing. In patients with PWS and an imprinting defect, the paternal chromosome carries a maternal imprint. In patients with AS and an imprinting defect, the maternal chromosome carries a paternal imprint. Imprinting defects offer a unique opportunity to identify some of the factors and mechanisms involved in imprint erasure, resetting and maintenance. In approximately 10% of cases the imprinting defects are caused by a microdeletion affecting the 5' end of the SNURF-SNRPN locus. These deletions define the 15q imprinting center (IC), which regulates imprinting in the whole domain. These findings have been confirmed and extended in knock-out and transgenic mice. In the majority of patients with an imprinting defect, the incorrect imprint has arisen without a DNA sequence change, possibly as the result of stochastic errors of the imprinting process or the effect of exogenous factors.
普拉德-威利综合征（PWS）和安吉尔曼综合征（AS）是两种不同的神经遗传性疾病，由人类15号染色体长臂近端印记基因功能丧失引起。在少数PWS和AS患者中，疾病是由于异常印记和基因沉默所致。在患有PWS和印记缺陷的患者中，父源染色体带有母源印记。在患有AS和印记缺陷的患者中，母源染色体带有父源印记。印记缺陷为识别参与印记擦除、重置和维持的一些因素及机制提供了独特机会。在大约10%的病例中，印记缺陷由影响SNURF-SNRPN基因座5'端的微缺失引起。这些缺失定义了15q印记中心（IC），其调节整个区域的印记。这些发现已在基因敲除和转基因小鼠中得到证实和扩展。在大多数患有印记缺陷的患者中错误的印记在没有DNA序列改变的情况下出现，可能是印记过程随机错误或外源性因素作用的结果。
