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Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma, and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants in\n                    <jats:italic>PIK3CD<\/jats:italic>\n                    and\n                    <jats:italic>PIK3R1<\/jats:italic>\n                    , both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function variants in the\u00a0\n                    <jats:italic>PIK3CD<\/jats:italic>\n                    \u00a0gene, while loss of function variants in\n                    <jats:italic>PIK3R1<\/jats:italic>\n                    have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. Despite available treatments, survival for individuals with APDS appears to be shortened from the average lifespan. A Kaplan\u2013Meier survival analysis for APDS showed the conditional survival rate at the age of 20 years was 87%, age of 30 years was 74%, and ages of 40 and 50 years were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The overall mortality rate for HSCT in APDS1 and APDS2 cases was 15.6%, while the mortality rate for lymphoma was 47.6%. This survival and mortality data illustrate that new treatments are needed to mitigate the risk of death from lymphoma and other cancers as well as infection. These analyses based on real-world evidence gathered from the medical literature comprise the largest study of survival and mortality for APDS to date.\n                  <\/jats:p>","DOI":"10.1007\/s10238-023-01259-y","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T06:02:21Z","timestamp":1706335341000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Systematic review of mortality and survival rates for APDS"],"prefix":"10.1007","volume":"24","author":[{"given":"Jennifer","family":"Hanson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope E.","family":"Bonnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"1259_CR1","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1126\/science.1243292","volume":"342","author":"I Angulo","year":"2013","unstructured":"Angulo I, Vadas O, Garcon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, et al. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342:866\u201371.","journal-title":"Science"},{"key":"1259_CR2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/ni.2771","volume":"15","author":"CL Lucas","year":"2014","unstructured":"Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15:88\u201397.","journal-title":"Nat Immunol"},{"key":"1259_CR3","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1084\/jem.20141759","volume":"211","author":"CL Lucas","year":"2014","unstructured":"Lucas CL, Zhang Y, Venida A, Wang Y, Hughes J, McElwee J, Butrick M, Matthews H, Price S, Biancalana M, et al. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med. 2014;211:2537\u201347.","journal-title":"J Exp Med"},{"key":"1259_CR4","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1172\/JCI75746","volume":"124","author":"MC Deau","year":"2014","unstructured":"Deau MC, Heurtier L, Frange P, Suarez F, Bole-Feysot C, Nitschke P, Cavazzana M, Picard C, Durandy A, Fischer A, et al. A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest. 2014;124:3923\u20138.","journal-title":"J Clin Invest"},{"key":"1259_CR5","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s12016-019-08738-9","volume":"59","author":"M Jamee","year":"2020","unstructured":"Jamee M, Moniri S, Zaki-Dizaji M, Olbrich P, Yazdani R, Jadidi-Niaragh F, Aghamahdi F, Abolhassani H, Condliffe AM, Aghamohammadi A, et al. 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