Ellaway C, Buchholz T, Smith A, Leonard H, Christodoulou J
Department of Paediatrics and Child Health, University of Sydney, New South Wales, Australia.
J Child Neurol. 1998 Sep;13(9):448-51. doi: 10.1177/088307389801300907.
Rett syndrome and Angelman syndrome are neurodevelopmental disorders characterized by severe intellectual disability, microcephaly, speech disturbance, movement disorders with gait and/or truncal ataxia, and occasionally a similar facial appearance. Both conditions can be difficult to diagnose in girls early in their clinical course and can be difficult to distinguish from each other. Genomic imprinting is a known association in Angelman syndrome and previously has been suggested in Rett syndrome. Our aim was to evaluate the methylation status in a cohort of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has not been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and confirm the phenotypic similarities between Rett syndrome and Angelman syndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome critical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in distinguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, however, does not exclude the diagnosis of Angelman syndrome and clear distinction between the two syndromes will evolve over time.
雷特综合征和安吉尔曼综合征是神经发育障碍性疾病，其特征为严重智力残疾、小头畸形、言语障碍、伴有步态和/或躯干共济失调的运动障碍，偶尔还有相似的面容。这两种病症在临床病程早期对女孩来说都难以诊断，且彼此之间难以区分。基因组印记是安吉尔曼综合征已知的关联因素，此前也曾有人提出其与雷特综合征有关。我们的目的是使用针对15号染色体q11 - 13区域的甲基化系统，评估一组典型雷特综合征患者的甲基化状态。此前尚未有关于雷特综合征15号染色体甲基化分析的报道。此外，我们记录了31名典型雷特综合征女孩的临床特征，并证实了雷特综合征与安吉尔曼综合征之间的表型相似性。这些雷特综合征女孩的甲基化研究结果正常。这排除了15号染色体（15q11 - 13）上安吉尔曼综合征关键区域的印记错误与雷特综合征的关联，表明甲基化研究可能有助于在具有重叠临床表型的年轻患者中区分雷特综合征和安吉尔曼综合征。然而，正常的甲基化模式并不能排除安吉尔曼综合征的诊断，随着时间推移，这两种综合征之间的明确区分将会逐渐清晰。
