Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage

• DOI: 10.1126/science.1243292
• Publication Date: 2013-10-18T02:25:20Z
• Authors: Ivan Angulo; Oscar Vadas; Fabien Garçon; Edward Banham-Hall; Vincent Plagnol; Timothy R. Leahy; Helen Baxendale; Tanya Coulter; James Curtis; Changxin Wu; Katherine Blake-P...; Olga Perisic; Deborah Smyth; Mailis Maes; Christine Fiddler; Jatinder Juss; Deirdre Cilliers; Gašper Markelj; Anita Chandra; George Farmer; Anna Kielkowska; Jonathan Clark; Sven Kracker; Marianne Debré; Capucine Picard; Isabelle Pellier; Nada Jabado; James A. Morris; Gabriela Barcenas...; Alain Fischer; Len Stephens; Phillip Hawkins; Jeffrey C. Barrett; Mario Abinun; Menna Clatworthy; Anne Durandy; Rainer Doffinger; Edwin R. Chilvers; Andrew J. Cant; Dinakantha Kumara...; Klaus Okkenhaug; Roger L. Williams; Alison Condliffe; Sergey Nejentsev
• Keywords: Class I Phosphatidylinositol 3-Kinases; Immunologic Deficiency Syndromes; Pedigree; 3. Good health; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 0302 clinical medicine; Phosphatidylinositol Phosphates; Mutation; Humans; Genetic Predisposition to Disease; Lymphocytes; Proto-Oncogene Proteins c-akt; Respiratory Tract Infections

Answers from Exomes

Exome sequencing, which targets only the protein-coding regions of the genome, has the potential to identify the underlying genetic causes of rare inherited diseases.

Angulo et al.

(p. 866 , published online 17 October; see Perspective by

Conley and Fruman

) performed exome sequencing of individuals from seven unrelated families with severe, recurrent respiratory infections. The patients carried the same mutation in the gene coding for the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). The mutation caused aberrant activation of this kinase, which plays a key role in immune cell signaling. Drugs inhibiting PI3Kδ are already in clinical trials for other disorders.