Japanese and North American/European patients with Beckwith–Wiedemann syndrome have different frequencies of some epigenetic and genetic alterations

Abstract

Beckwith -Wiedemann syndrome (BWS) is an imprinting-related human disease. The frequencies of causative alterations such as loss of methylation (LOM) of KvDMR1, hypermethylation of H19-DMR, paternal uniparental disomy, CDKN1C gene mutation, and chromosome abnormality have been described for North American and European patients, but the corresponding frequencies in Japanese patients have not been measured to date. Analysis of 47 Japanese cases of BWS revealed a significantly lower frequency of H19-DMR hypermethylation and a higher frequency of chromosome abnormality than in North American and European patients. These results suggest that susceptibility to epigenetic and genetic alterations differs between the two groups.

Beckwith–Wiedemann syndrome and uniparental disomy 11p: fine mapping of the recombination breakpoints and evaluation of several techniques

“…Sequences of the primers were obtained from the NCBI public database (http://www.ncbi.nlm.nih.gov/sites/entrez). We calculated the percentage of mosaicism as recommended by Sasaki et al 34 The calculation was as follows: (KÀ1)/(K+1) Â 100; where K is the ratio of the intensity of the parental alleles (paternal/maternal ratio) of the test sample.…”

Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome: Opposite Phenotypes with Heterogeneous Molecular Etiology

“…Other minor features are neonatal hypoglycemia, hemihyperplasia, and characteristic facial features. A rec- [Kotzot et al, 1995;Eggermann et al, 1997;Preece et al, 1997;Netchine et al, 2007;Abu-Amero et al, 2008;Binder et al, 2008] Methylation abnormality at ICR1 in the 11p15 region hypomethylation in 37 -63% [Netchine et al, 2007;Binder et al, 2008;Bartholdi et al, 2009;Bruce et al, 2009;Abu-Amero et al, 2010;Turner et al, 2010;Vals et al, 2015b] hypermethylation 5 -10% [Gaston et al, 2001;Cooper et al, 2005Cooper et al, , 2007Sasaki et al, 2007] Methylation abnormality at ICR2 in the 11p15 region few cases with the hypomethylation of both ICRs [Begemann et al, 2011] hypomethylation in 50 -60% [Gaston et al, 2001;Cooper et al, 2005;Weksberg et al, 2010;Begemann et al, 2012b] Duplication in the 11p15 region (may involve ICR1 and/or ICR2) maternal 1 -2% [Eggermann et al, 2010a[Eggermann et al, , 2014b paternal microdeletions involving ICR1 (~5%) and microduplications of ICR2 (<1%) [Niemitz et al, 2004;Sparago et al, 2004;Bliek et al, 2009b;Demars et al, 2011;Begemann et al, 2012b;Vals et al, 2015a] Other chromosomal aberrations (including cryptic) 2% (the most frequent are 1q21 microdeletion, 12q24 microdeletion, ring chromosome 15, and deletion 15qter) [Bruce et al, 2010;Spengler et al, 2012;Fuke et al, 2013;Fokstuen and Kotzot, 2014;Azzi et al, 2015] rare cases, maternally inherited balanced translocations/inversions …”

“…The centromeric ICR2 in the 11p15 region controls the KCNQ1 (potassium channel KQTfamily member) cluster, the maternally expressed KCNQ1 and CDKN1C , and the paternally expressed KCNQ1QT1 gene. DNA methylation defects involving ICR1 usually cause SRS (loss of methylation in 37-63% of the cases) but can also cause BWS (gain of methylation in 5-10% of the cases) [Gaston et al, 2001;Cooper et al, 2005Cooper et al, , 2007Sasaki et al, 2007]. Some of these methylation alterations have been associated with genomic alterations [Niemitz et al, 2004;Sparago et al, 2004;Prawitt et al, 2005].…”

Towards Further Optimization of Preimplantation Embryo Culture Media: from the Viewpoint of Omics and Somatic Cell Nuclear Transfer (SCNT) Studies

“…However, ART conceptions are reported to be associated with an increased incidence of congenital abnormalities, low birthweight and preterm birth when compared with spontaneous conceptions [4], and there are concerns that in vitro culture potentially causes transcriptomic changes [5], and epigenetic adverse effects on preimplantation embryo development (e.g. Beckwith-Wiedemann syndrome [6][7][8][9], Angelman syndrome [10][11][12][13][14][15], Prader-Willi syndrome [15], Silver-Russell synderome [15], Retinoblastoma [16][17][18], and congenital abnormalities [4]), as well as having a significant effect on the birthweight of offspring [19,20].…”