@article{09f026b1f9cf49eebf8586bff60a0a61,
title = "EIF2AK4 Mutations in pulmonary capillary hemangiomatosis",
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 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.",
author = "Best, {D. Hunter} and Sumner, {Kelli L.} and Austin, {Eric D.} and Chung, {Wendy K.} and Brown, {Lynette M.} and Borczuk, {Alain C.} and Rosenzweig, {Erika B.} and Pinar Bayrak-Toydemir and Rong Mao and Cahill, {Barbara C.} and Tazelaar, {Henry D.} and Leslie, {Kevin O.} and Hemnes, {Anna R.} and Robbins, {Ivan M.} and Elliott, {C. Gregory}",
note = "Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Brown is employed by Intermountain Healthcare (IHC Health Services, Inc). In the last 2 years IHC Health Services, Inc has received compensation from Ikaria Inc for a clinical trial contract for which Dr Brown is the principal investigator. In addition, Dr Brown has received compensation for time and travel from United Therapeutics for attendance at advisory board meetings. Dr Elliott is employed by Intermountain Healthcare (IHC Health Services, Inc). In the last 3 years IHC Health Services, Inc has received compensation for clinical trial contracts (on which Dr Elliott is the Principal Investigator) from Actelion Pharmaceuticals Ltd, Bayer Corp, GeNo, Gilead, and United Therapeutics Corp. IHC Health Service Inc has also received or will receive compen sation from LungRx for Dr Elliott's travel and consultancy on the BEAT study. During this same time period, Dr Elliott received compensation for time and travel from Ikaria Inc as chair of the steering committee for the INOPulse study and from Co-Therix as a steering committee member. Dr Rosenzweig has received honoraria for advisory panels from Actelion Pharmaceuticals Ltd and United Therapeutics Corp in the past 3 years and is a consultant for Ikaria, Inc on a clinical research trial. Dr Bayrak- Toydemir is employed by ARUP Laboratories. Dr Hemnes has received research funding from the National Institutes of Health, United Therapeutics Corp, and Pfizer Inc, and has served as a consultant to Actelion Pharmaceuticals Ltd, Pfizer Inc, and United Therapeutics Corp. Drs Best, Austin, Chung, Borczuk, Mao, Cahill, Tazelaar, Leslie, and Robbins and Ms Sumner have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Funding Information: Funding/Support: This research was supported in part by the National Institutes of Health [K23 HL098743; R01 HL060056; NIH 1P01HL108800-0] and Intermountain Research and Medical Foundation [1007044]. ",
year = "2014",
month = feb,
doi = "10.1378/chest.13-2366",
language = "English (US)",
volume = "145",
pages = "231--236",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "2",
}