Editors' ChoiceGENETICS

Answers from Exomes

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Science Signaling  19 Nov 2013:
Vol. 6, Issue 302, pp. ec282
DOI: 10.1126/scisignal.2004921

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. (see the 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.

I. Angulo, O. Vadas, F. Garçon, E. Banham-Hall, V. Plagnol, T. R. Leahy, H. Baxendale, T. Coulter, J. Curtis, C. Wu, K. Blake-Palmer, O. Perisic, D. Smyth, M. Maes, C. Fiddler, J. Juss, D. Cilliers, G. Markelj, A. Chandra, G. Farmer, A. Kielkowska, J. Clark, S. Kracker, M. Debré, C. Picard, I. Pellier, N. Jabado, J. A. Morris, G. Barcenas-Morales, A. Fischer, L. Stephens, P. Hawkins, J. C. Barrett, M. Abinun, M. Clatworthy, A. Durandy, R. Doffinger, E. R. Chilvers, A. J. Cant, D. Kumararatne, K. Okkenhaug, R. L. Williams, A. Condliffe, S. Nejentsev, Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science 342, 866–871 (2013). [Abstract][Full Text]

M. E. Conley, D. A. Fruman, Can cancer drugs treat immunodeficiency? Science 342, 814–815 (2013). [Abstract][Full Text]