Glenn C C, Driscoll D J, Yang T P, Nicholls R D
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville 32610, USA.
Mol Hum Reprod. 1997 Apr;3(4):321-32. doi: 10.1093/molehr/3.4.321.
The Prader-Willi (PWS) and Angelman (AS) syndromes are two clinically distinct syndromes which result from lack of expression of imprinted genes within chromosome 15q11-q13. These two syndromes result from 15q11-q13 deletions, chromosome 15 uniparental disomy (UPD), imprinting centre mutations and, for AS, probable mutations in a single gene. The differential phenotype results from a paternal genetic deficiency in PWS patients and a maternal genetic deficiency in AS patients. Within 15q11-q13, four genes (SNRPN, IPW, ZNF127, FNZ127) and two expressed sequence tags (PAR1 and PAR5) have been found to be expressed only from the paternally inherited chromosome, and therefore all must be considered candidate genes involved in the pathogenesis of PWS. A candidate AS gene (UBE3A) has very recently been identified. The mechanisms of imprinted gene expression are not yet understood, but it is clear that DNA methylation is involved in both somatic cell expression and inheritance of the imprint. The presence of DNA methylation imprints that distinguish the paternally and maternally inherited alleles is a common characteristic of all known imprinted genes which have been studied extensively, including SNRPN and ZNF127. Recently, several PWS and AS patients have been found that have microdeletions in a region upstream of the SNRPN gene referred to as the imprinting centre, or IC. Paternal IC deletions in PWS patients and maternal IC deletions in AS patients result in uniparental DNA methylation and uniparental gene expression at biparentally inherited loci. The IC is a novel genetic element which controls initial resetting of the parental imprint in the germline for all imprinted gene expression over a 1.5-2.5 Mb region within chromosome 15q11-q13.
普拉德-威利（PWS）综合征和安吉尔曼（AS）综合征是两种临床症状不同的综合征，它们是由15号染色体q11-q13区域内印记基因表达缺失所致。这两种综合征由15q11-q13缺失、15号染色体单亲二体性（UPD）、印记中心突变引起，对于AS综合征来说，还可能由单个基因的突变导致。PWS患者的差异表型源于父系遗传缺陷，而AS患者的差异表型源于母系遗传缺陷。在15q11-q13区域内，已发现四个基因（SNRPN、IPW、ZNF127、FNZ127）和两个表达序列标签（PAR1和PAR5）仅从父系遗传的染色体上表达，因此所有这些都必须被视为与PWS发病机制相关的候选基因。最近已鉴定出一个候选AS基因（UBE3A）。印记基因表达的机制尚不清楚，但很明显DNA甲基化参与了体细胞表达和印记的遗传。区分父系和母系遗传等位基因的DNA甲基化印记的存在是所有已被广泛研究的已知印记基因的共同特征，包括SNRPN和ZNF127。最近，发现了一些PWS和AS患者，他们在SNRPN基因上游一个称为印记中心或IC的区域存在微缺失。PWS患者的父系IC缺失和AS患者的母系IC缺失导致双亲遗传位点的单亲DNA甲基化和单亲基因表达。印记中心是一种新的遗传元件，它控制着15号染色体q11-q13区域内1.5-2.5 Mb范围内所有印记基因表达的种系中亲本印记的初始重置。
