• Przemyslaw Szafranski, Avinash V Dharmadhikari, Jennifer A Wambach, Chris T Towe, Frances V White, R Mark Grady, Pirooz Eghtesady, F Sessions Cole, Gail Deutsch, Partha Sen, and Paweł Stankiewicz.
• Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
• Am. J. Med. Genet. A. 2014 Aug 1; 164A (8): 2013-9.

AbstractPosition effects due to disruption of distant cis-regulatory regions have been reported for over 40 human gene loci; however, the underlying mechanisms of long-range gene regulation remain largely unknown. We report on two patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) caused by overlapping genomic deletions that included a distant FOXF1 transcriptional enhancer mapping 0.3 Mb upstream to FOXF1 on 16q24.1. In one patient with atypical late-onset ACDMPV, a ∼1.5 Mb deletion removed the proximal 43% of this enhancer, leaving the lung-specific long non-coding RNA (lncRNA) gene LINC01081 intact. In the second patient with severe neonatal-onset ACDMPV, an overlapping ∼194 kb deletion disrupted LINC01081. Both deletions arose de novo on maternal copy of the chromosome 16, supporting the notion that FOXF1 is paternally imprinted in the human lungs. RNAi-mediated knock-down of LINC01081 in normal fetal lung fibroblasts showed that this lncRNA positively regulates FOXF1 transcript level, further indicating that decrease in LINC01081 expression can contribute to development of ACDMPV.© 2014 Wiley Periodicals, Inc.

32 keywords...

hide…