SNP and DNA Methylation Analyses of a Monozygotic Twins Discordant for Complete Endocardial Cushion Defect: a Case Report

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Dec 12

PMID 36505317

Authors

Bihui Bao

Hua Hu

Limei Chen

Shiyong Lu

Qifeng Tang

Zhiqing Liang

Affiliations

Soon will be listed here.

Abstract

The exact cause of complete endocardial cushion defect (ECD) is still unknown. This report describes a unique pair of monozygotic twins (MZ twins) discordant for ECD. The chromosome karyotyping analysis revealed normal karyotype of 46, XY, 16qh+ and mat in both MZ twins. A genome-wide analysis of DNA using the Affymetrix SNP 6.0 revealed identical genotyping of single nucleotide polymorphisms (SNPs) and copy number variations (CNVs). An extensive methylation assay was carried out by NimbleGen 3 × 720 K CpG Island Plus RefSeq Promoter Arrays to analyze the potential epigenetic differences. The DNA methylation profiles of the affected twin seemed increased compared with that of the unaffected twin. However, further validation of Notch1 promoter hypermethylation and six top-ranked differentially methylated CpG sites by sodium bisulfate modification and methylation-specific PCR, failed to reveal consistent methylation differences between the twins. Other relevant factors, such as heritability and penetrance of the condition that place the MZ twins near to a threshold for ECD or variations in local epigenetic events in the twins' heart tissues, are probably responsible for the phenotypic discordance.

References

de la Pompa J, Epstein J . Coordinating tissue interactions: Notch signaling in cardiac development and disease. Dev Cell. 2012; 22(2):244-54. PMC: 3285259. DOI: 10.1016/j.devcel.2012.01.014. View

Hartman R, Riehle-Colarusso T, Lin A, Frias J, Patel S, Duwe K . Descriptive study of nonsyndromic atrioventricular septal defects in the National Birth Defects Prevention Study, 1997-2005. Am J Med Genet A. 2011; 155A(3):555-64. DOI: 10.1002/ajmg.a.33874. View

McPherson E, Korlesky C, Hebbring S . Cardiac Anomalies in Liveborn and Stillborn Monochorionic Twins. Clin Med Res. 2020; 18(2-3):58-67. PMC: 7428205. DOI: 10.3121/cmr.2019.1478. View

Li D, Hallett M, Zhu W, Rubart M, Liu Y, Yang Z . Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis. Development. 2010; 138(2):303-15. PMC: 3005605. DOI: 10.1242/dev.055566. View

Imany-Shakibai H, Yin O, Russell M, Sklansky M, Satou G, Afshar Y . Discordant congenital heart defects in monochorionic twins: Risk factors and proposed pathophysiology. PLoS One. 2021; 16(5):e0251160. PMC: 8101911. DOI: 10.1371/journal.pone.0251160. View

Hoohenkerk G, Bruggemans E, Rijlaarsdam M, Schoof P, Koolbergen D, Hazekamp M . More than 30 years' experience with surgical correction of atrioventricular septal defects. Ann Thorac Surg. 2010; 90(5):1554-61. DOI: 10.1016/j.athoracsur.2010.06.008. View

Karbarz M . Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels. Genes (Basel). 2020; 11(9). PMC: 7563277. DOI: 10.3390/genes11090977. View

Wong C, Caspi A, Williams B, Craig I, Houts R, Ambler A . A longitudinal study of epigenetic variation in twins. Epigenetics. 2010; 5(6):516-26. PMC: 3322496. DOI: 10.4161/epi.5.6.12226. View

Greenway S, Pereira A, Lin J, DePalma S, Israel S, Mesquita S . De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nat Genet. 2009; 41(8):931-5. PMC: 2747103. DOI: 10.1038/ng.415. View

10.

Priest J, Girirajan S, Vu T, Olson A, Eichler E, Portman M . Rare copy number variants in isolated sporadic and syndromic atrioventricular septal defects. Am J Med Genet A. 2012; 158A(6):1279-84. PMC: 3564951. DOI: 10.1002/ajmg.a.35315. View

11.

Scacheri P, Crawford G, Davis S . Statistics for ChIP-chip and DNase hypersensitivity experiments on NimbleGen arrays. Methods Enzymol. 2006; 411:270-82. DOI: 10.1016/S0076-6879(06)11014-9. View

12.

Bruder C, Piotrowski A, Gijsbers A, Andersson R, Erickson S, Diaz De Stahl T . Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet. 2008; 82(3):763-71. PMC: 2427204. DOI: 10.1016/j.ajhg.2007.12.011. View

13.

Oster M, Riehle-Colarusso T, Alverson C, Correa A . Associations between maternal fever and influenza and congenital heart defects. J Pediatr. 2011; 158(6):990-5. DOI: 10.1016/j.jpeds.2010.11.058. View

14.

Abu-Halima M, Weidinger J, Poryo M, Henn D, Keller A, Meese E . Micro-RNA signatures in monozygotic twins discordant for congenital heart defects. PLoS One. 2019; 14(12):e0226164. PMC: 6894838. DOI: 10.1371/journal.pone.0226164. View

15.

Dempster E, Pidsley R, Schalkwyk L, Owens S, Georgiades A, Kane F . Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet. 2011; 20(24):4786-96. PMC: 3221539. DOI: 10.1093/hmg/ddr416. View

16.

Wang Y, Wu B, Chamberlain A, Lui W, Koirala P, Susztak K . Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development. PLoS One. 2013; 8(4):e60244. PMC: 3613384. DOI: 10.1371/journal.pone.0060244. View

17.

Bao B, Zhang L, Hu H, Yin S, Liang Z . Deletion of a single-copy DAAM1 gene in congenital heart defect: a case report. BMC Med Genet. 2012; 13:63. PMC: 3482563. DOI: 10.1186/1471-2350-13-63. View

18.

Kaplan L, Foster R, Shen Y, Parry D, McMaster M, OLeary M . Monozygotic twins discordant for neurofibromatosis 1. Am J Med Genet A. 2010; 152A(3):601-6. PMC: 2830382. DOI: 10.1002/ajmg.a.33271. View

19.

Riley M, McBride K, Cole S . NOTCH1 missense alleles associated with left ventricular outflow tract defects exhibit impaired receptor processing and defective EMT. Biochim Biophys Acta. 2010; 1812(1):121-9. PMC: 3180902. DOI: 10.1016/j.bbadis.2010.10.002. View

20.

van den Akker N, Caolo V, Molin D . Cellular decisions in cardiac outflow tract and coronary development: an act by VEGF and NOTCH. Differentiation. 2012; 84(1):62-78. DOI: 10.1016/j.diff.2012.04.002. View