Epigenetics and genomics in Turner syndrome

Viuff, Mette; Skakkebæk, Anne; Nielsen, Morten Muhlig; Chang, Simon; Gravholt, Claus Højbjerg

doi:10.1002/ajmg.c.31683

Cited by 41 publications

(33 citation statements)

References 80 publications

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“…Network analysis found that KDM6A is a key regulator in Turner syndrome [116]. KDM6A is a potential candidate gene for premature ovarian failure in Turner syndrome [117,118] because of its role in fertility and pluripotency (Section 2.3), and may be involved in gonadal dysgenesis [119].…”

Section: Kdm6a In Genetic Conditionsmentioning

confidence: 99%

Lysine demethylases KDM6A and UTY: The X and Y of histone demethylation

Gažová

Lengeling

Summers

2019

Molecular Genetics and Metabolism

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Histone demethylases remove transcriptional repressive marks from histones in the nucleus. KDM6A (also known as UTX) is a lysine demethylase which acts on the trimethylated lysine at position 27 in histone 3. The KDM6A gene is located on the X chromosome but escapes X inactivation even though it is not located in the pseudoautosomal region. There is a homologue of KDM6A on the Y chromosome, known as UTY. UTY was thought to have lost its demethylase activity and to represent a non-functional remnant of the ancestral KDM6A gene. However, results with knockout mice suggest that the gene is expressed and the protein performs some function within the cell. Female mice with homozygous deletion of Kdm6a do not survive, but hemizygous males are viable, attributed to the presence of the Uty gene. KDM6A is mutated in the human condition Kabuki syndrome type 2 (OMIM 300867) and in many cases of cancer. The amino acid sequence of KDM6A has been conserved across animal phyla, although it is only found on the X chromosome in eutherian mammals. In this review, we reanalyse existing data from various sources (protein sequence comparison, evolutionary genetics, transcription factor binding and gene expression analysis) to determine the function, expression and evolution of KDM6A and UTY and show that UTY has a functional role similar to KDM6A in metabolism and development.

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Section: Kdm6a In Genetic Conditionsmentioning

confidence: 99%

Lysine demethylases KDM6A and UTY: The X and Y of histone demethylation

Gažová

Lengeling

Summers

2019

Molecular Genetics and Metabolism

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“…Defining the contribution of specific X-linked genes in abnormal Turner phenotypes is a work in progress. For example, the escape genes KDM6A and TIMP1 are hypothesized to be involved in premature ovarian failure and aortic aneurysm formation, respectively (Trolle et al, 2016; Viuff et al, 2019). Recent screens of X-linked copy number variation (CNV) in cohorts of healthy women and those with primary ovarian insufficiency (POI) show a high prevalence of deletions encompassing escape genes as well as lncRNAs (Yatsenko et al, 2019).…”

Section: Role Of X-linked Genes In Sex Differences and In Diseasementioning

confidence: 99%

X Inactivation and Escape: Epigenetic and Structural Features

Distèche

Berletch

2019

Front. Cell Dev. Biol.

105

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X inactivation represents a complex multi-layer epigenetic mechanism that profoundly modifies chromatin composition and structure of one X chromosome in females. The heterochromatic inactive X chromosome adopts a unique 3D bipartite structure and a location close to the nuclear periphery or the nucleolus. X-linked lncRNA loci and their transcripts play important roles in the recruitment of proteins that catalyze chromatin and DNA modifications for silencing, as well as in the control of chromatin condensation and location of the inactive X chromosome. A subset of genes escapes X inactivation, raising questions about mechanisms that preserve their expression despite being embedded within heterochromatin. Escape gene expression differs between males and females, which can lead to physiological sex differences. We review recent studies that emphasize challenges in understanding the role of lncRNAs in the control of epigenetic modifications, structural features and nuclear positioning of the inactive X chromosome. Second, we highlight new findings about the distribution of genes that escape X inactivation based on single cell studies, and discuss the roles of escape genes in eliciting sex differences in health and disease.

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“…The specific comorbidities for women with Turner syndrome such as infertility, cardiac malformations, bone dysgenesis, and autoimmune diseases may depend on a complex relationship between genes as well as transcriptional and epigenetic factors affecting gene expression across the genome [19]. Risks during pregnancy include aortic disorders, hepatic disease, thyroid disease, type 2 diabetes, and cesarean section delivery [3].…”

Section: Genetic Consultmentioning

confidence: 99%

IVF and ICSI outcomes of female patients with X chromosome mosaicism: A 5-year retrospective cohort study

Liang

Yang

et al. 2020

Preprint

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BackgroundThis study focused on the assisted reproductive treatment (ART) outcomes of female patients with X chromosome mosaicism (XM), who underwent their first IVF/ICSI and day 2 or day3 fresh embryo transfer, and the possible impacts of the different mosaic types.Results78 couples with XM female and normal male were included as the X group. 78 couples with normal karyotype were included as the control group. Subgroup X1 included 41 45,X/46,XX cases, Subgroup X2 included 23 47,XXX/46,XX cases, and Subgroup X3 included 13 45,X/47,XXX/46,XX cases. With similar female age and similar body mass index (BMI), the X group had higher total gonadotropin (Gn) dosage than the control group (1800 IU VS 1612 IU). In subgroup analysis, the follical number during oocyte retrieval was less in subgroup X1 than that in X2 or X3. The fertilization rate was lower in subgroup X1 than that in subgroup X2. The utilization rate was higher in subgroup X2 than that in subgroup X3. The implantation rate, clinical pregnancy rate, and miscarriage rate before 12 weeks' gestation were similar in all groups.ConclusionsFemale with 45,X cell line may face higher Gn dosage, less follical number during oocyte retrieval and fewer embryos. But female with X chromosome mosaicism may have similar clinical pregnancy rate and miscarriage rate after fresh embryo transfer.

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Epigenetics and genomics in Turner syndrome

Cited by 41 publications

References 80 publications

Lysine demethylases KDM6A and UTY: The X and Y of histone demethylation

Lysine demethylases KDM6A and UTY: The X and Y of histone demethylation

X Inactivation and Escape: Epigenetic and Structural Features

IVF and ICSI outcomes of female patients with X chromosome mosaicism: A 5-year retrospective cohort study

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