DNA Methylation Analysis of Turner Syndrome BAV

Gutierrez, Jacob; Davis, Brett A.; Nevonen, Kimberly A.; Ward, Samantha; Carbone, Lucia; Maslen, Cheryl L.

doi:10.3389/fgene.2022.872750

Cited by 4 publications

(2 citation statements)

References 81 publications

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“…Individuals with TS have global hypomethylation of their genome, with differential expression of autosomal genes suggesting that Xchr deficiency has genome-wide implications (Trolle et al 2016 ). Furthermore, another recent study that compared differentially-methylated genes in individuals with TS and BAV, individuals with TS without BAV, and 46,XX individuals with non-syndromic BAV demonstrated significantly more differentially-methylated regions between individuals with TS with BAV and the 46,XX BAV individuals, which is consistent with a larger impact of Xchr monosomy on the epigenetic landscape (Gutierrez et al 2022 ).…”

Section: Introductionmentioning

confidence: 67%

CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome

et al. 2023

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Turner syndrome (TS) is a chromosomal disorder caused by complete or partial loss of the second sex chromosome and exhibits phenotypic heterogeneity, even after accounting for mosaicism and karyotypic variation. Congenital heart defects (CHD) are found in up to 45 percent of girls with TS and span a phenotypic continuum of obstructive left-sided lesions, with bicuspid aortic valve (BAV) being the most common. Several recent studies have demonstrated a genome-wide impact of X chromosome haploinsufficiency, including global hypomethylation and altered RNA expression. The presence of such broad changes to the TS epigenome and transcriptome led others to hypothesize that X chromosome haploinsufficiency sensitizes the TS genome, and several studies have demonstrated that a second genetic hit can modify disease susceptibility in TS. The objective of this study was to determine whether genetic variants in known heart developmental pathways act synergistically in this setting to increase the risk for CHD, specifically BAV, in TS. We analyzed 208 whole exomes from girls and women with TS and performed gene-based variant enrichment analysis and rare-variant association testing to identify variants associated with BAV in TS. Notably, rare variants in CRELD1 were significantly enriched in individuals with TS who had BAV compared to those with structurally normal hearts. CRELD1 is a protein that functions as a regulator of calcineurin/NFAT signaling, and rare variants in CRELD1 have been associated with both syndromic and non-syndromic CHD. This observation supports the hypothesis that genetic modifiers outside the X chromosome that lie in known heart development pathways may influence CHD risk in TS.

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Section: Introductionmentioning

confidence: 67%

CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome

et al. 2023

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“…As mentioned earlier, patients with TS are at increased risk of cardiac abnormalities, which is a risk factor for early death in these patients, and it is estimated that 30% of women with TS have a bicuspid aortic valve. This could be conditioned by differences in gene expression 17 .…”

Section: Changes In Gene Expressionmentioning

confidence: 99%

Molecular mechanisms of early development of 45,X0 embryos (Turner syndrome)

Espinosa-Ahedo

2024

PERE

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Clinical practice guidelines for the care of girls and women with Turner syndrome

Gravholt,

Andersen,

Christin-Maitre

et al. 2024

European Journal of Endocrinology

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Turner syndrome affects 50 per 100,000 females, affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and US culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: 1) diagnosis and genetics, 2) growth, 3) puberty and estrogen treatment, 4) cardiovascular health, 5) transition, 6) fertility assessment, monitoring, and counselling, 7) health surveillance for comorbidities throughout the lifespan, and 8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

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DNA Methylation Analysis of Turner Syndrome BAV

Cited by 4 publications

References 81 publications

CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome

CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome

Molecular mechanisms of early development of 45,X0 embryos (Turner syndrome)

Clinical practice guidelines for the care of girls and women with Turner syndrome

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