Fridman C, Hosomi N, Varela M C, Souza A H, Fukai K, Koiffmann C P
Department of Biology, University of São Paulo, São Paulo, Brazil.
Am J Med Genet A. 2003 Jun 1;119A(2):180-3. doi: 10.1002/ajmg.a.20105.
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation, speech impairment, ataxia, and happy disposition with frequent smiling. AS results from the loss of expression of a maternal imprinted gene, UBE3A, mapped within 15q11-q13 region, due to different mechanisms: maternal deletion, paternal UPD, imprinting center mutation, and UBE3A mutation. Deletion AS patients may exhibit hypopigmentation of skin, eye, and hair correlating with deletion of P gene localized in the distal part of Prader-Willi (PWS)/AS region. Our patient presented developmental delay, severe mental retardation, absence of speech, outbursts of laughter, microcephaly, ataxia, hyperactivity, seizures, white skin, no retinal pigmentation, and gold yellow hair. His parents were of African ancestry. The SNURF-SNRPN methylation analysis confirmed AS diagnosis and microsatellite studies disclosed deletion with breakpoints in BP2 and BP3. All of the 25 exons and flanking introns of the P gene of the patient, his father, and mother were investigated. The patient is hemizygous for the deleted exon 7 of the P gene derived from his father who is a carrier of the deleted allele. Our patient manifests OCA2 associated with AS due to the loss of the maternal chromosome 15 with the normal P allele, and the paternal deletion in the P gene. As various degrees of hypopigmentation are associated with PWS and AS patients, the study of the P gene in a hemizygous state could contribute to the understanding of its effect on human pigmentation during development and to disclose the presence of modifier pigmentation gene(s) in the PWS/AS region.
天使综合征（AS）是一种神经发育障碍，其特征为智力迟钝、言语障碍、共济失调以及常伴有频繁微笑的愉悦性情。AS是由于位于15q11-q13区域的母系印记基因UBE3A因不同机制导致表达缺失所致，这些机制包括母系缺失、父系单亲二倍体、印记中心突变以及UBE3A突变。缺失型AS患者可能会出现皮肤、眼睛和头发色素减退，这与位于普拉德-威利综合征（PWS）/AS区域远端的P基因缺失相关。我们的患者表现出发育迟缓、严重智力迟钝、无言语能力、阵阵笑声、小头畸形、共济失调、多动、癫痫发作、皮肤白皙、无视网膜色素沉着以及金黄色头发。他的父母是非洲裔。SNURF-SNRPN甲基化分析证实了AS诊断，微卫星研究揭示了在BP2和BP3处有断点的缺失。对患者及其父母的P基因的所有25个外显子和侧翼内含子进行了研究。患者对于来自其父亲（父亲是缺失等位基因的携带者）的P基因缺失外显子7是半合子状态。我们的患者由于携带正常P等位基因的母系15号染色体缺失以及P基因的父系缺失，表现出与AS相关的OCA2。由于不同程度的色素减退与PWS和AS患者相关，对半合子状态下P基因的研究可能有助于理解其在发育过程中对人类色素沉着的影响，并揭示PWS/AS区域中修饰色素沉着基因的存在。
