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

TLDR

Exome sequencing can uncover genetic causes of rare inherited diseases, and PI3Kδ inhibitors are already in clinical trials for other disorders. The authors performed exome sequencing on individuals from seven unrelated families with severe, recurrent respiratory infections. All patients carried the same mutation in the PI3Kδ catalytic subunit, leading to aberrant kinase activation that disrupts immune cell signaling. Angulo et al.

Abstract

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.