Two deletions overlapping a distantFOXF1enhancer unravel the role of lncRNALINC01081in etiology of alveolar capillary dysplasia with misalignment of pulmonary veins
| Autor: | Frances V. White, Przemyslaw Szafranski, R. Mark Grady, Pirooz Eghtesady, Pawel Stankiewicz, Partha Sen, Jennifer A. Wambach, Gail H. Deutsch, Avinash V. Dharmadhikari, F. Sessions Cole, Chris T. Towe |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Alveolar capillary dysplasia Biopsy DNA Mutational Analysis Gene Expression Biology Persistent Fetal Circulation Syndrome Article Chromosome 16 RNA interference Gene expression Genetics medicine Humans RNA Messenger Enhancer Lung Gene Genetics (clinical) Sequence Deletion Regulation of gene expression Comparative Genomic Hybridization Infant Newborn Forkhead Transcription Factors medicine.disease Molecular biology Radiography Enhancer Elements Genetic Female RNA Interference RNA Long Noncoding Genomic imprinting |
| Zdroj: | American Journal of Medical Genetics Part A. 164:2013-2019 |
| ISSN: | 1552-4825 |
| Popis: | Position 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. |
| Databáze: | OpenAIRE |
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