Jan 22, 2015

Rare variants in RTEL1 are associated with familial interstitial pneumonia

American Journal of Respiratory and Critical Care Medicine
Joy D CoganTimothy S Blackwell


Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected c...Continue Reading

  • References35
  • Citations57


  • References35
  • Citations57


Mentioned in this Paper

Trichohepatoenteric Syndrome
Pathogenic Aspects
Biochemical Pathway
Mononuclear Cells
Peripheral Blood
Peripheral Blood Mononuclear Cells (Lab Test)
Pulmonary Fibrosis

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