Entrez Gene Summary for MAGT1 Gene:

Relevance of MAGT1 in XMEN disease:

Mutations in the MAGT1 gene cause XMEN disease. XMEN disease is a rare genetic disorder  of the immune system  that illustrates the role of Mg2+  in cell signaling . XMEN stands for “X-linked immunodeficiency  with magnesium defect, Epstein-Barr virus  (EBV) infection, andneoplasia .” It is characterized by CD4 lymphopenia , severe chronic viral infections, and defective T-lymphocyte activation. Investigators in the laboratory of Dr. Michael Lenardo, National Institute of Allergy and Infectious Diseases  at the National Institutes of Health  first described this condition in 2011. [1] [2] [3]

XMEN is caused by loss of function mutations  in the gene  MAGT1 .[1] MAGT1 is a 70 kb gene with 10 exons  encoding for a 335 amino acid protein that maps to Xq13.1-q13.2. The protein serves as a magnesium-specific transporter and is known to play an essential role in magnesium homeostasis . MAGT1 is evolutionarily conserved  and expressed in all mammalian cells with higher expression inhematopoietic  lineages. XMEN patients have been found to carry bothMAGT1 deletions  and missense  mutations. However, the severity of thephenotype  is not entirely explained by the genotype . The disease severity also likely depends on environmental and other genetic factors. [3]

XMEN follows an X-linked inheritance  pattern because the MAGT1 is located on the X chromosome . In X-linked inheritance, generally, men are affected and women are carriers. This is in contrast to the inheritance of traits on autosomal chromosomes , where both sexes have the same probability of being affected. In X-linked inheritance, all offspring of a carrier female have a 50% chance of inheriting the mutation if the father does not also carry the mutation. This means about half of male offspring from a carrier mother will be affected and about half of female offspring will be carriers. None of the sons and all of the daughters of an affected male will inherit the mutation. Those daughters will be carriers and not affected themselves. Mothers of XMEN patients exhibit preferential X chromosome inactivation  of the chromosome with the mutation in their hematopoietic cells and are asymptomatic .

Clinically, XMEN patients have splenomegaly , chronic Epstein Barr Virus (EBV) infection, and are developmentally normal. They have an increased susceptibility for developing EBV+lymphoma . Additionally, XMEN patients have excessive infections consistent with the underlying immunodeficiency . These infections included recurrent otitis media , sinusitis , viral pneumonia , diarrhea, upper respiratory infections ,epiglottitis , and pertussis . Although autoimmune  symptoms do not feature prominently in XMEN autoimmune cytopenias  were observed in two unrelated patients. [3]

Regarding laboratory findings, XMEN patients generally have chronically high levels of EBV with increased EBV-infected cells, diminished thymic output of CD4+ cells, reduced CD4:CD8 ratio, moderately high B cell  counts, and mild neutropenia . Their neutropenia may be related to their chronic EBV. Some patients also showed defective T cell proliferation in response to mitogen stimulation, variable immunoglobulin  deficiencies, or deficient vaccination response. [2] [1] [3]

Disease relevance of RP11-217H1.1

• Whereas specimens after steel implantation revealed a diffuse siderosis of connective tissue cells, those after titanium exhibited occasionally a focal siderosis due to implantation-associated bleeding [4].

High impact information on RP11-217H1.1

• Implantation-associated changes in bovine uterine expression of integrins and extracellular matrix [5].
• Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line [6].
• No implantation-associated peak was identified for estrogens or progesterone and mean values of progesterone and estrone were actually greater in female serum samples collected during summer than fall [7].
• Group 1 underwent an echocardiogram, treadmill exercise, and quality of life measurement 1 month prior to and 6 months following AV node ablation and pacemaker implantation associated with discontinuation of rate-control medications [8].
• METHODS: Sixteen Hydrophilic Acrylic foldable intraocular lenses from 14 patients who presented with decreased visual acuity from 6 months to 1 year after normal phacoemulsification and IOL implantation associated with extensive transparent change on optic of the lens [9].

Analytical, diagnostic and therapeutic context of RP11-217H1.1

• U.G.H. syndrome is a known complication of IOL implantation associated with the use of anterior and rarely, posterior chamber intraocular lenses [10].

References