Details

Autor(en) / Beteiligte

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

Titel

EIF2AK4 Mutations in Pulmonary Capillary Hemangiomatosis

Ist Teil von

• Chest, 2014-02, Vol.145 (2), p.231-236

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.