Division of Human Genetics, University of Southampton School of Medicine, Southampton SO16 6YD, UK.
Am J Med Genet A. 2010 Aug;152A(8):1990-3. doi: 10.1002/ajmg.a.33530.
This study was an investigation of 90 patients referred to the Wessex Regional Genetics Laboratory for and negative by molecular cytogenetic analysis using array comparative genomic hybridization. This patient cohort represents typical referrals to a regional genetic centre. Methylation analysis was performed at 13 imprinted loci [PLAGL1, IGF2R, MEST, GRB10, H19, IGF2 DMR2 (IGF2P0), KCNQ1OT1 (KvDMR), MEG3, SNRPN, PEG3, GNAS (GNAS exon 1a and NESP55) and GNASAS]. In total 6/90 (6.67%) were shown to have a methylation defect, 2 of which were associated with known imprinting disorders: 1 patient had isolated hypomethylation at IGF2P0, an atypical epigenotype associated with Russell-Silver syndrome, and 1 showed hypomethylation at KvDMR consistent with a diagnosis of Beckwith-Wiedemann syndrome. A further 4 patients, 3 exhibiting complete hypermethylation, and 1 partial hypomethylation, had aberrations at IGF2R, the clinical significance of which remains unclear. This study demonstrates the potential utility of epigenetic investigation in routine diagnostic testing.
本研究调查了 90 名患者，他们因分子细胞遗传学分析呈阴性而被转介到 Wessex 地区遗传实验室进行 array 比较基因组杂交分析。该患者队列代表了对区域遗传中心的典型转诊。在 13 个印迹基因座 [PLAGL1、IGF2R、MEST、GRB10、H19、IGF2 DMR2（IGF2P0）、KCNQ1OT1（KvDMR）、MEG3、SNRPN、PEG3、GNAS（GNAS 外显子 1a 和 NESP55）和 GNASAS] 上进行了甲基化分析。总共发现 6/90（6.67%）例存在甲基化缺陷，其中 2 例与已知的印迹障碍有关：1 例患者 IGF2P0 存在孤立性低甲基化，这是与 Russell-Silver 综合征相关的非典型表型，1 例患者 KvDMR 存在低甲基化，符合 Beckwith-Wiedemann 综合征的诊断。另外 4 例患者，3 例表现为完全甲基化过度，1 例表现为部分低甲基化，在 IGF2R 上存在异常，其临床意义尚不清楚。本研究表明了表观遗传学研究在常规诊断检测中的潜在应用价值。
