Epigenetic control of the immune system: a lesson from Kabuki syndrome

Stagi, Stefano; Gulino, Anna Virginia; Lapi, Elisabetta; Rigante, Donato

doi:10.1007/s12026-015-8707-4

Cited by 54 publications

(64 citation statements)

References 95 publications

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“…Recent gene expression profiling suggests alterations in TS immune cells and, in particular, highlighted reduced T cell expression of UTX, which may lead to decreased Tfh cells in TS. Of note, genetic deficiency of the UTX gene results in the genetic disorder Kabuki syndrome (KS), a rare congenital disorder that is also associated with recurrent OM [19••, 20]. Furthermore, reduced immunoglobulin levels, hypogammaglobulinemia, poor vaccine response, and reduced memory T and B lymphocytes have also been reported in KS [40, 41].…”

Section: Discussionmentioning

confidence: 99%

“…A total of 1169 unique genes showed differential expression in TS PBMCs, including 35 on the X chromosome. In particular, ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX, encoded by Utx or Kdm6a located at Xp11.3 [20]) was among the top 10 X-linked genes with the largest decrease in expression and the only gene among these candidates that escapes X inactivation [21]. …”

Section: Ts Patient Immune Cells Express Decreased Utx a Histone-modmentioning

confidence: 99%

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Epigenetic Dysfunction in Turner Syndrome Immune Cells

Thrasher

Hong

Whitmire

et al. 2016

Curr Allergy Asthma Rep

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Turner syndrome (TS) is a chromosomal condition associated with partial or complete absence of the X chromosome that involves characteristic findings in multiple organ systems. In addition to well-known clinical characteristics such as short stature and gonadal failure, TS is also associated with T cell immune alterations and chronic otitis media, suggestive of a possible immune deficiency. Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a downregulated gene in TS immune cells. Importantly, UTX is an X-linked gene that escapes X-chromosome inactivation and thus is haploinsufficient in TS. Mice with T cell-specific UTX deficiency have impaired clearance of chronic viral infection due to decreased frequencies of T follicular helper (Tfh) cells, which are critical for B cell antibody generation. In parallel, TS patients have decreased Tfh frequencies in peripheral blood. Together, these findings suggest that haploinsufficiency of the X-linked UTX gene in TS T cells underlies an immune deficit, which may manifest as increased predisposition to chronic otitis media.

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Section: Discussionmentioning

confidence: 99%

Section: Ts Patient Immune Cells Express Decreased Utx a Histone-modmentioning

confidence: 99%

Epigenetic Dysfunction in Turner Syndrome Immune Cells

Thrasher

Hong

Whitmire

et al. 2016

Curr Allergy Asthma Rep

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“…Two of the most common features are intellectual disability and growth abnormalities. 2,20,21 The majority of the genes defective in disorders of the epigenetic machinery are located on autosomal chromosomes, but the rest (~20%) are X-linked. 16,17 In fact, a disproportionately high number of genes related to intellectual disability encode for protein components of the epigenetic transcription regulation.…”

Section: Mendelian Disorders Of the Epigenetic Machinerymentioning

confidence: 99%

“…Other rarer features may include cleft lip and/or palate, congenital heart defects (especially coarctation of the aorta), genitourinary anomalies, and anal atresia. 20 We have also provided characteristics of all currently known epigenetic factors to aid in such prioritization (available at www.epigeneticmachinery.org). The protein encoded by KMT2D is a histone methyltransferase.…”

Section: Examples Of Mendelian Disorders Of the Epigenetic Machinerymentioning

confidence: 99%

Clinical epigenetics: a primer for the practitioner

Aygün

Björnsson

2019

Develop Med Child Neuro

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ARTAssistive reproductive technology BWSBeckwith-Wiedemann syndrome MLIDMulti-locus imprinting disorder PWS Prader-Willi syndrome SRS Silver-Russell syndrome TND Transient neonatal diabetes Disruption of epigenetic modifications and the factors that maintain these modifications is rapidly emerging as a cause of developmental disorders. Here we summarize some of the major principles of epigenetics including how epigenetic modifications are: (1) normally reset in the germ line, (2) form an additional layer of interindividual variation, (3) are environmentally sensitive, and (4) change over time in humans. We also briefly discuss the disruption of growth and intellect associated with the Mendelian disorders of the epigenetic machinery and the classical imprinting disorders (such as Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, and Angelman syndrome), as well as suggesting some diagnostic considerations for the clinicians taking care of these patients. Finally, we discuss novel therapeutic strategies targeting epigenetic modifications, which may offer a safe alternative to up and coming genome editing strategies for the treatment of genetic diseases. This review provides a starting point for clinicians interested in epigenetics and the role epigenetic disruption plays in human disease.

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“…The genetic causes of the disease are diverse mutations in the KDM2T or in KDM6A genes that encode proteins histone modifiers which play an important role in immune system and embryogenic development;[19] however, how pathological molecular pathways influence in development remains unclear. [8]…”

Section: Introductionmentioning

confidence: 99%

Carotid artery occlusion in Kabuki syndrome: Case report and literature review

et al. 2017

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Background:Kabuki syndrome is a rare multiple congenital anomaly syndrome whose main diagnostic findings are craniofacial phenotypic changes and mental retardation. Organic structural lesions in the central nervous system are rare, although have been described already. Systemic vascular changes have also been reported rarely.Case Description:We report the case of a young patient with Kabuki syndrome who had a transient ischemic attack due to dissection of the internal carotid artery and a likely gliosis area on the white matter.Conclusion:Association of cervical arterial disease with this syndrome has never been described, and its pathophysiology is not yet established; however, it can direct future research and maybe treatment.

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Epigenetic control of the immune system: a lesson from Kabuki syndrome

Cited by 54 publications

References 95 publications

Epigenetic Dysfunction in Turner Syndrome Immune Cells

Epigenetic Dysfunction in Turner Syndrome Immune Cells

Clinical epigenetics: a primer for the practitioner

Carotid artery occlusion in Kabuki syndrome: Case report and literature review

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