Greger V, Knoll J H, Wagstaff J, Woolf E, Lieske P, Glatt H, Benn P A, Rosengren S S, Lalande M
Genetics Division, Children's Hospital, Boston, MA 02115-5737, USA.
Am J Hum Genet. 1997 Mar;60(3):574-80.
Angelman syndrome (AS) most frequently results from large (> or = 5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located approximately 25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within approximately 1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype.
天使综合征（AS）最常见的病因是15号染色体q11-q13区域发生大于或等于5兆碱基（Mb）的新发缺失。这些缺失均源自母亲，也有少数关于15号染色体父源单亲二体的病例报道。后一发现表明，AS是由于印记的15q11-q13区域缺乏母源贡献所致。未能继承父源15q11-q13区域会导致临床上截然不同的普拉德-威利综合征。已观察到因易位或臂间倒位导致的AS病例与缺失有关，且尚无关于AS中平衡重排的确切报道。我们报告了首例此类病例，涉及一个臂内倒位，其断点位于参考标记D15S10近端约25千碱基（kb）处。该倒位遗传自表型正常的母亲。在此病例中，通过使用定位到倒位断点约1 kb范围内的克隆片段进行分子分析，未发现明显缺失。文中讨论了几种假说来解释倒位与AS表型之间的关系。
