@article {771,
	title = {Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease.},
	journal = {J Clin Invest},
	volume = {130},
	year = {2020},
	month = {2020 01 02},
	pages = {507-522},
	abstract = {<p>X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the magnesium transporter 1 (MAGT1) gene. We studied 23 patients with XMEN, 8 of whom were EBV naive. We observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), and increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to the previously described features of an inverted CD4/CD8 ratio, CD4+ T lymphocytopenia, increased B cells, dysgammaglobulinemia, and decreased expression of the natural killer group 2, member D (NKG2D) receptor. EBV-associated B cell malignancies occurred frequently in EBV-infected patients. We studied patients with XMEN and patients with autoimmune lymphoproliferative syndrome (ALPS) by deep immunophenotyping (32 immune markers) using time-of-flight mass cytometry (CyTOF). Our analysis revealed that the abundance of 2 populations of naive B cells (CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4++CD10+CD38+ and CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4+CD10-CD38-) could differentially classify XMEN, ALPS, and healthy individuals. We also performed glycoproteomics analysis on T lymphocytes and show that XMEN disease is a congenital disorder of glycosylation that affects a restricted subset of glycoproteins. Transfection of MAGT1 mRNA enabled us to rescue proteins with defective glycosylation. Together, these data provide new clinical and pathophysiological foundations with important ramifications for the diagnosis and treatment of XMEN disease.</p>},
	keywords = {Antigens, CD, Autoimmune Lymphoproliferative Syndrome, Cation Transport Proteins, CD4-CD8 Ratio, Female, Glycosylation, Humans, Magnesium Deficiency, Male, X-Linked Combined Immunodeficiency Diseases},
	issn = {1558-8238},
	doi = {10.1172/JCI131116},
	author = {Ravell, Juan C and Matsuda-Lennikov, Mami and Chauvin, Samuel D and Zou, Juan and Biancalana, Matthew and Deeb, Sally J and Price, Susan and Su, Helen C and Notarangelo, Giulia and Jiang, Ping and Morawski, Aaron and Kanellopoulou, Chrysi and Binder, Kyle and Mukherjee, Ratnadeep and Anibal, James T and Sellers, Brian and Zheng, Lixin and He, Tingyan and George, Alex B and Pittaluga, Stefania and Powers, Astin and Kleiner, David E and Kapuria, Devika and Ghany, Marc and Hunsberger, Sally and Cohen, Jeffrey I and Uzel, Gulbu and Bergerson, Jenna and Wolfe, Lynne and Toro, Camilo and Gahl, William and Folio, Les R and Matthews, Helen and Angelus, Pam and Chinn, Ivan K and Orange, Jordan S and Trujillo-Vargas, Claudia M and Franco, Jose Luis and Orrego-Arango, Julio and Guti{\'e}rrez-Hincapi{\'e}, Sebastian and Patel, Niraj Chandrakant and Raymond, Kimiyo and Patiroglu, Turkan and Unal, Ekrem and Karakukcu, Musa and Day, Alexandre Gr and Mehta, Pankaj and Masutani, Evan and De Ravin, Suk S and Malech, Harry L and Altan-Bonnet, Gr{\'e}goire and Rao, V Koneti and Mann, Matthias and Lenardo, Michael J}
}
@article {231,
	title = {The Alu-rich genomic architecture of SPAST predisposes to diverse and functionally distinct disease-associated CNV alleles.},
	journal = {Am J Hum Genet},
	volume = {95},
	year = {2014},
	month = {2014 Aug 07},
	pages = {143-61},
	abstract = {<p>Intragenic copy-number variants (CNVs) contribute to the allelic spectrum of both Mendelian and complex disorders. Although pathogenic deletions and duplications in SPAST (mutations in which cause autosomal-dominant spastic paraplegia 4 [SPG4]) have been described, their origins and molecular consequences remain obscure. We mapped breakpoint junctions of 54 SPAST CNVs at nucleotide resolution. Diverse combinations of exons are deleted or duplicated, highlighting the importance of particular exons for spastin function. Of the 54 CNVs, 38 (70\%) appear to be mediated by an Alu-based mechanism, suggesting that the Alu-rich genomic architecture of SPAST renders this locus susceptible to various genome rearrangements. Analysis of breakpoint Alus further informs a model of Alu-mediated CNV formation characterized by small CNV size and potential involvement of mechanisms other than homologous recombination. Twelve deletions (22\%) overlap part of SPAST and a portion of a nearby, directly oriented gene, predicting novel chimeric genes in these subjects{\textquoteright} genomes. cDNA from a subject with a SPAST final exon deletion contained multiple SPAST:SLC30A6 fusion transcripts, indicating that SPAST CNVs can have transcriptional effects beyond the gene itself. SLC30A6 has been implicated in Alzheimer disease, so these fusion gene data could explain a report of spastic paraplegia and dementia cosegregating in a family with deletion of the final exon of SPAST. Our findings provide evidence that the Alu genomic architecture of SPAST predisposes to diverse CNV alleles with distinct transcriptional--and possibly phenotypic--consequences. Moreover, we provide further mechanistic insights into Alu-mediated copy-number change that are extendable to other loci.</p>},
	keywords = {Adenosine Triphosphatases, Alu Elements, Base Sequence, Cation Transport Proteins, Cell Line, Transformed, DNA Copy Number Variations, Genotype, Humans, Protein Isoforms, Recombinant Fusion Proteins, Sequence Analysis, DNA, Sequence Deletion, Spastic Paraplegia, Hereditary, Spastin},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2014.06.014},
	author = {Boone, Philip M and Yuan, Bo and Campbell, Ian M and Scull, Jennifer C and Withers, Marjorie A and Baggett, Brett C and Beck, Christine R and Shaw, Christine J and Stankiewicz, Pawel and Moretti, Paolo and Goodwin, Wendy E and Hein, Nichole and Fink, John K and Seong, Moon-Woo and Seo, Soo Hyun and Park, Sung Sup and Karbassi, Izabela D and Batish, Sat Dev and Ord{\'o}{\~n}ez-Ugalde, Andr{\'e}s and Quint{\'a}ns, Beatriz and Sobrido, Mar{\'\i}a-Jes{\'u}s and Stemmler, Susanne and Lupski, James R}
}
