Premium
Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell–Silver syndrome
Author(s) -
Horike ShinIchi,
Ferreira Jose Carlos P.,
MeguroHorike Makiko,
Choufani Sanaa,
Smith Adam C.,
Shuman Cheryl,
Meschino Wendy,
Chitayat David,
Zackai Elaine,
Scherer Stephen W.,
Weksberg Rosanna
Publication year - 2009
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.33065
Subject(s) - epigenetics , dna methylation , genomic imprinting , methylation , biology , imprinting (psychology) , genetics , uniparental disomy , epigenomics , chromosome , chromosome 7 (human) , dna , gene , karyotype , gene expression
Abstract Over a 10‐year period blood samples were collected from 57 individuals with growth restriction and RSS‐like features. Our goal was to identify epigenetic abnormalities in this cohort, including uniparental disomy of chromosome 7 (UPD7), methylation changes at chromosome11p15, as well as new epigenomic alterations. We evaluated the methylation status of 7 imprinting control regions on chromosomes 7, 11, 14, and 15. UPD7 and chromosome 7 structural abnormalities had been previously identified in five patients. Epigenetic alterations on chromosome 11p15 were identified in 11 patients. Of interest, in 3 of these 11 patients, the epigenetic alterations were limited to the H19 promoter and the distal region of its associated imprinting center, ICR1. In addition, in one patient, we detected methylation changes consistent with maternal UPD at all tested imprinted regions. This patient series suggests that epimutations on chromosome 11p15 can be most efficiently detected in RSS patients by screening for DNA methylation defects at the H19 promoter or the distal region of ICR. © 2009 Wiley‐Liss, Inc.