EIF2AK4 Mutations in pulmonary capillary hemangiomatosis

D. Hunter Best, Kelli L. Sumner, Eric D. Austin, Wendy K. Chung, Lynette M. Brown, Alain C. Borczuk, Erika B. Rosenzweig, Pinar Bayrak-Toydemir, Rong Mao, Barbara C. Cahill, Henry D. Tazelaar, Kevin O. Leslie, Anna R. Hemnes, Ivan M. Robbins, C. Gregory Elliott

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Background: Pulmonary capillary hemangiomatosis (PCH) is a rare disease of capillary proliferation of unknown cause and with a high mortality. Families with multiple affected individuals with PCH suggest a heritable cause although the genetic etiology remains unknown. Methods: We used exome sequencing to identify a candidate gene for PCH in a family with two affected brothers. We then screened 11 unrelated patients with familial (n 5 1) or sporadic (n 5 10) PCH for mutations. Results: Using exome sequencing, we identifi ed compound mutations in eukaryotic translation initiation factor 2 a kinase 4 ( EIF2AK4 ) (formerly known as GCN2 ) in both affected brothers. Both parents and an unaffected sister were heterozygous carriers. In addition, we identifi ed two EIF2AK4 mutations in each of two of 10 unrelated individuals with sporadic PCH. EIF2AK4 belongs to a family of kinases that regulate angiogenesis in response to cellular stress. Conclusions: Mutations in EIF2AK4 are likely to cause autosomal-recessive PCH in familial and some nonfamilial cases. CHEST 2014; 145(2):231-236.

Original languageEnglish (US)
Pages (from-to)231-236
Number of pages6
Issue number2
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine


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