Random X chromosome inactivation in patients with Klinefelter syndrome

Kinjo, Kenichi; Yoshida, Tomoko; Kobori, Yoshitomo; Okada, Hiroshi; Suzuki, Erina; Ogata, Tsutomu; Miyado, Mami; Fukami, Maki

doi:10.1186/s40348-020-0093-x

Cited by 10 publications

(7 citation statements)

References 18 publications

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“…Asprosin level is also elevated in obese children more significantly than in overweight children, with girls having higher levels than boys [ 35 ]. The current review of the literature in this area has been prepared by Janoschek et al [ 36 ]. On the basis of these findings, asprosin seems to be a factor favoring both the development of obesity and accompanying diseases such as DM2, while promoting the development of insulin resistance.…”

Section: Asprosin and Insulin Resistance Diabetes And Obesitymentioning

confidence: 99%

Asprosin—A Fasting-Induced, Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity, Diabetes, or Infertility? A Review of the Literature

Mazur-Biały

2021

Nutrients

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Asprosin is a recently discovered protein released during fasting conditions mainly by adipocytes from white adipose tissue. As a glucogenic peptide, it stimulates the release of glucose from hepatic cells by binding to the OLFR734 receptor and leading to the activation of the G protein-cAMP-PKA pathway. As it crosses the blood–brain barrier, it also acts as an orexigenic peptide that stimulates food intake through activation of AgRP neurons in the hypothalamus; thus, asprosin participates in maintaining the body’s energy homeostasis. Moreover, studies have shown that asprosin levels are pathologically elevated in obesity and related diseases. However, the administration of anti-asprosin antibodies can both normalize its concentration and reduce food intake in obese mice, which makes it an interesting factor to combat obesity and related diseases. Current research also draws attention to the relationship between asprosin and fertility, especially in men. Asprosin improves age- and obesity-related decrease in fertility potential by improving sperm motility. It should also be mentioned that plasma asprosin levels can be differentially modulated by physical activity; intense anaerobic exercise increases asprosin level, while aerobic exercise decreases it. However, further research is necessary to confirm the exact mechanisms of asprosin activity and its potential as a therapeutic target.

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Section: Asprosin and Insulin Resistance Diabetes And Obesitymentioning

confidence: 99%

Asprosin—A Fasting-Induced, Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity, Diabetes, or Infertility? A Review of the Literature

Mazur-Biały

2021

Nutrients

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“…Part of this dosage compensation system is the transcriptional silencing of one X in the somatic cells of females via the epigenetic process of XCI (2). In XXX human females, two Xs are inactivated (22), and in XXY males one X is silenced, leaving one active X (23,24). This is a reflection of the counting mechanism of XCI, which results in all but one X being silenced in mammals (25) and is entirely genotype dependent.…”

Section: Discussionmentioning

confidence: 99%

Both phenotypic and genotypic sex influence sex chromosome dosage compensation in a sex reversing lizard

Hanrahan,

Chang,

Lister

et al. 2023

Preprint

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Studies of sex chromosome dosage compensation have historically focussed on therian mammals which have a conserved XY sex determination system. In contrast, lizards have sex determination systems that can differ between even closely related species that include XY and ZW systems and thermolabile systems where genetic and temperature interact to various degrees to determine sex. The eastern three-lined skink (Bassiana duperreyi) has a differentiated XY sex determination system, in which low temperature incubation during development can cause female to male sex reversal, producing XX males. This provides a unique opportunity to investigate how genotype and phenotype affect dosage compensation. We generated transcriptomes from brain and heart tissue of normal adult males and females, along with brain tissue of sex-reversed XX males. We observed partial dosage compensation between XX females and XY males in both brain and heart, with median gene expression from the X in normal males being 0.7 times that of normal females. Surprisingly, in brain of sex reversed XX males the median X chromosome output did not match that of either normal males or females, but instead was 0.89 times that of the normal XX female level. This suggests that not just genotype, but also sexual phenotype, influences gene dosage of the X chromosome. This has profound implications for our understanding of the evolution of dosage compensation.

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“…It has been suggested that SXI in KS patients occurs as a common genetic event ( Iitsuka et al, 2001 ). However, it has also been shown that 10–50% of KS patients present SXI ( Amos-Landgraf et al, 2006 ; Bojesen et al, 2011 ; Mehta et al, 2012 ; Kinjo et al, 2020 ). Our data show similar results to these studies.…”

Section: Discussionmentioning

confidence: 99%

Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern

et al. 2021

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Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development (GTPBP6, EIF2S3, ITM2A, HUWE1, KDM5C, GDI1, and VAMP7) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than the four individuals who presented a skewed X-inactivation (SXI) pattern. The evaluation of gene expression showed higher GTPBP6 expression in KS patients with RXI than in controls (p = 0.0059). Interestingly, the expression of GTPBP6 in KS patients with SXI did not differ from that observed in controls. Therefore, our data suggest for the first time that GTPBP6 expression is negatively associated with full-scale IQ under the regulation of the type of XCI pattern. The SXI pattern may regulate GTPBP6 expression, thereby dampening the impairment in cognitive performance and playing a role in intelligence variability in individuals with KS, which warrants further mechanistic investigations.

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Random X chromosome inactivation in patients with Klinefelter syndrome

Cited by 10 publications

References 18 publications

Asprosin—A Fasting-Induced, Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity, Diabetes, or Infertility? A Review of the Literature

Asprosin—A Fasting-Induced, Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity, Diabetes, or Infertility? A Review of the Literature

Both phenotypic and genotypic sex influence sex chromosome dosage compensation in a sex reversing lizard

Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern

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