ETA2022 Oral Presentations Oral Session 8: Basic 2 (5 abstracts)
Stochastic epigenetic mutations as possible explanation for phenotypical discordance among twins with congenital hypothyroidism
Marina Muzza 1 , Davide Gentilini 2 , Tiziana de Filippis 1 , Luciano Calzari 3 , Maria Cristina Vigone 4 , Giovanna Weber 4 , Alessandra Cassio 5 , Antonella Olivieri 6 & Luca Persani 7
1Istituto Auxologico Italiano Irccs, Division of Endocrine and Metabolic Diseases, Milan, Italy; 2Istituto Auxologico Italiano, University of Pavia, Bioinformatics and Statistical Genomics Unit; Department of Brain and Behavioral Sciences, Milan; Pavia, Italy; 3Istituto Auxologico Italiano Irccs, Bioinformatics and Statistical Genomics Unit, Milan, Italy; 4San Raffaele Hospital Irccs, Encocrine Unit, Milan, Italy; 5University of Bologna, Department of Pediatric Endocrinology, Bologna, Italy; 6Italian National Institute of Health, Department of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Roma, Italy; 7Istituto Auxologico Italiano Irccs, University of Milan, Division of Endocrine and Metabolic Diseases; Department of Medical Biotechnology and Translational Medicine, Milan, Italy
Congenital Hypothyroidism (CH) is the most common congenital endocrine disease and avoidable cause of severe mental retardation. The CH pathogenesis may include the contribution of genetic and environmental factors. However, causal mutations have been found in a minority of cases. Moreover, the elevated frequency of discordance for CH phenotype between monozygotic (MZ) twins suggests the involvement of non-Mendelian mechanisms. Aim of this study was to investigate the role of epigenetics in CH pathogenesis. We performed a genome-wide DNA methylation analysis in the peripheral whole blood of 23 twin pairs (10 monozygotic and 13 dizygotic), of whom 4 concordant and 19 discordant for CH at birth, using the Illumina HumanMethylation450K BeadChip array. Differential methylation analysis failed to identify differences in methylation levels between cases and controls. In order to detect rare epigenetic differences not shared among subjects, we then analyzed the distribution of Stochastic Epigenetic Mutations (SEMs). Interestingly, the median number of hypomethylated SEMs resulted significantly increased in cases compared to controls, independently from the zygosity, the thyroid morphology, the CH outcome or the genetic background. The prioritization analysis for CH performed on the genes that were epimutated exclusively in cases identified SLC26A4, FOXI1, NKX2-5 and TSHB as the genes with the highest score. Furthermore, the analysis of significantly SEM-enriched region led to the identification of two genes (FAM50B and MEG8) that were epigenetically dysregulated in cases. Collectively our data indicate that epigenetic modifications are rare events in CH pathology. However, a significant increase of hypomethylated SEMs was identified in hypothyroid twin pairs, suggesting that thyroid defects could be caused by an increased expression of predisposing factors. The role of genes that resulted epigenetically dysregulated in CH cases should be further investigated.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more