EIF2AK4 Mutations in Pulmonary Capillary Hemangiomatosis

Overview

Journal Chest

Publisher Elsevier

Specialty Pulmonary Medicine

Date 2013 Oct 19

PMID 24135949

Citations 81

Authors

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

Affiliations

Soon will be listed here.

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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