Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1016/j.jaci.2014.03.025 http://scihub22266oqcxt.onion/10.1016/j.jaci.2014.03.025 C4132167!4132167!24797421     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Allergy+Clin+Immunol 2014 ; 133 (6): 1667-75 Nephropedia Template TP {{tp|p=24797421|t=2014. Somatic reversion in DOCK8 immunodeficiency modulates disease phenotype |pdf=|usr=}}{{24797421}} gab.com Text Somatic reversion in DOCK8 immunodeficiency modulates disease phenotype JO: J Allergy Clin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=24797421 #FOAvip Background: Autosomal recessive, loss-of-function mutations in DOCK8 cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking. Objective: We investigated whether reversions contributed to the variable disease expression. Methods: Patients followed at the NIH Clinical Center were studied. We performed detailed genetic analyses and intracellular flow cytometry to detect DOCK8 protein expression within lymphocyte subsets. Results: We identified 17 out of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion due to somatic repair. Somatic repair of the DOCK8 mutations resulted from second-site mutation, original-site mutation, gene conversion, and intragenic crossover. Higher degrees of reversion were associated with recombination-mediated repair. DOCK8 expression was restored primarily within antigen-experienced T cells or in NK cells, but less so in naïve T cells or B cells. Several patients exhibited multiple different repair events. Patients who had reversions were older and had less severe allergic disease, although infection susceptibility persisted. No patients were cured without hematopoietic cell transplantation. Conclusions: In DOCK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair. Those patients had an ameliorated disease course with longer survival, but still had fatal complications or required hematopoietic cell transplantation. These observations support the concept that some DOCK8 immunodeficient patients have mutable mosaic genomes that may modulate disease phenotype over time. Twit Text FOAVip Somatic reversion in DOCK8 immunodeficiency modulates disease phenotype ????J Allergy Clin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=24797421 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24797421 #FOAvip English Wikipedia <ref>{{Cite pmid|24797421}}</ref> Somatic reversion in DOCK8 immunodeficiency modulates disease phenotype #MMPMID24797421 Jing H; Zhang Q; Zhang Y; Hill BJ; Dove CG; Gelfand EW; Atkinson TP; Uzel G; Matthews HF; Mustillo PJ; Lewis DB; Kavadas FD; Hanson IC; Kumar AR; Geha RS; Douek DC; Holland SM; Freeman AF; Su HC J Allergy Clin Immunol 2014[Jun]; 133 (6): 1667-75 PMID24797421show ga Background: Autosomal recessive, loss-of-function mutations in DOCK8 cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking. Objective: We investigated whether reversions contributed to the variable disease expression. Methods: Patients followed at the NIH Clinical Center were studied. We performed detailed genetic analyses and intracellular flow cytometry to detect DOCK8 protein expression within lymphocyte subsets. Results: We identified 17 out of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion due to somatic repair. Somatic repair of the DOCK8 mutations resulted from second-site mutation, original-site mutation, gene conversion, and intragenic crossover. Higher degrees of reversion were associated with recombination-mediated repair. DOCK8 expression was restored primarily within antigen-experienced T cells or in NK cells, but less so in naïve T cells or B cells. Several patients exhibited multiple different repair events. Patients who had reversions were older and had less severe allergic disease, although infection susceptibility persisted. No patients were cured without hematopoietic cell transplantation. Conclusions: In DOCK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair. Those patients had an ameliorated disease course with longer survival, but still had fatal complications or required hematopoietic cell transplantation. These observations support the concept that some DOCK8 immunodeficient patients have mutable mosaic genomes that may modulate disease phenotype over time. äSomatic reversion in DOCK8 immunodeficiency modulates disease phenotyp(epmc).pdf DeepDyve Pubget Overpricing