Investigation of 90 Patients Referred for Molecular Cytogenetic Analysis Using aCGH Uncovers Previously Unsuspected Anomalies of Imprinting

被引:7
作者
Poole, Rebecca L. [1 ,2 ]
Baple, Emma [3 ]
Crolla, John A. [1 ,4 ]
Temple, I. Karen [2 ,5 ]
Mackay, Deborah J. G. [1 ,2 ]
机构
[1] Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury SP2 8BJ, Wilts, England
[2] Univ Southampton, Sch Med, Div Human Genet, Southampton S016 6YD, Hants, England
[3] St Georges NHS Healthcare Trust, Dept Med Genet, London SW17 0QT, England
[4] Salisbury Dist Hosp, WRGL, Natl Genet Reference Lab Wessex, Salisbury SP2 8BJ, Wilts, England
[5] Southampton Univ Hosp Trust, Princess Anne Hosp, Wessex Clin Genet Serv, Southampton S016 5YA, Hants, England
关键词
imprinting; Russell Silver syndrome; Beckwith-Wiedemann syndrome; array comparative genomic hybridization; METHYLATION ANALYSIS; RECEPTOR GENE; GROWTH; HYPOMETHYLATION; OVERGROWTH; MUTATIONS; REVEALS; MOUSE; LOCI;
D O I
10.1002/ajmg.a.33530
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 [PLAG1, IGF2R, MEST, GRB10, H19, IGF2 DMR2 (IGF2P0), KCNQ1OT1 (KvDMR), MEG3, SNRPN, PEG3, GNAS (GNAS exon la 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. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:1990 / 1993
页数:4
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