Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K

• Published in: The Journal of experimental medicine Vol. 211; no. 13; pp. 2537 - 2547
• Main Authors: Lucas, Carrie L., Zhang, Yu, Venida, Anthony, Wang, Ying, Hughes, Jason, McElwee, Joshua, Butrick, Morgan, Matthews, Helen, Price, Susan, Biancalana, Matthew, Wang, Xiaochuan, Richards, Michael, Pozos, Tamara, Barlan, Isil, Ozen, Ahmet, Rao, V. Koneti, Su, Helen C., Lenardo, Michael J.
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 15.12.2014
• Subjects: Adolescent; Adult; Alternative Splicing - genetics; Antibody Formation; Base Sequence; Catalytic Domain; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation; Child, Preschool; Enzyme Activation; Exons - genetics; Female; Genes, Dominant; Heterozygote; Humans; Immunologic Deficiency Syndromes - enzymology; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Lymphoproliferative Disorders - enzymology; Lymphoproliferative Disorders - genetics; Lymphoproliferative Disorders - immunology; Male; Molecular Sequence Data; Mutation - genetics; Pedigree; Phosphatidylinositol 3-Kinases - chemistry; Phosphatidylinositol 3-Kinases - genetics; Protein Structure, Tertiary; Sequence Deletion; Signal Transduction; Telomere - metabolism; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism

Class IA phosphatidylinositol 3-kinases (PI3K), which generate PIP3 as a signal for cell growth and proliferation, exist as an intracellular complex of a catalytic subunit bound to a regulatory subunit. We and others have previously reported that heterozygous mutations in PIK3CD encoding the p110δ c...