2. Academic Validation
  3. EIF2AK4 mutations in pulmonary capillary hemangiomatosis

EIF2AK4 mutations in pulmonary capillary hemangiomatosis

  • Chest. 2014 Feb;145(2):231-236. doi: 10.1378/chest.13-2366.
D Hunter Best 1,  Kelli L Sumner 2,  Eric D Austin 3,  Wendy K Chung 4,  Lynette M Brown 5,  Alain C Borczuk 6,  Erika B Rosenzweig 4,  Pinar Bayrak-Toydemir 2,  Rong Mao 2,  Barbara C Cahill 7,  Henry D Tazelaar 8,  Kevin O Leslie 8,  Anna R Hemnes 9,  Ivan M Robbins 9,  C Gregory Elliott 10
Affiliations

Affiliations

  • 1 Department of Pathology, The University of Utah, Salt Lake City, UT; ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, UT.
  • 2 ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, UT.
  • 3 Department of Pathology, The University of Utah, Salt Lake City, UT; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
  • 4 Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY.
  • 5 Department of Medicine, School of Medicine, and Pulmonary Division, The University of Utah, Salt Lake City, UT; Department of Medicine, Intermountain Medical Center, Intermountain Healthcare, Murray, UT.
  • 6 Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY.
  • 7 Department of Medicine, The University of Utah, Salt Lake City, UT.
  • 8 Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Mayo Foundation for Medical Education and Research, Scottsdale, AZ.
  • 9 Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.
  • 10 Department of Medicine, School of Medicine, and Pulmonary Division, The University of Utah, Salt Lake City, UT; Department of Medicine, Intermountain Medical Center, Intermountain Healthcare, Murray, UT. Electronic address: greg.elliott@imail.org.
PMID: 24135949 DOI: 10.1378/chest.13-2366
Abstract

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 = 1) or sporadic (n = 10) PCH for mutations.

Results: Using exome Sequencing, we identified compound mutations in eukaryotic translation initiation factor 2 α kinase 4 (EIF2AK4) (formerly known as GCN2) in both affected brothers. Both parents and an unaffected sister were heterozygous carriers. In addition, we identified 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.

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