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Investigation of 90 patients referred for molecular cytogenetic analysis using aCGH uncovers previously unsuspected anomalies of imprinting
Author(s) -
Poole Rebecca L.,
Baple Emma,
Crolla John A.,
Temple I. Karen,
Mackay Deborah J.G.
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33530
Subject(s) - gnas complex locus , beckwith–wiedemann syndrome , genomic imprinting , epigenetics , dna methylation , uniparental disomy , methylation , genetics , imprinting (psychology) , comparative genomic hybridization , biology , bioinformatics , oncology , medicine , karyotype , gene , genome , gene expression , chromosome
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. © 2010 Wiley‐Liss, Inc.