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We postulated that in these patients, hitherto undetected pathogenic mutations might occur in regulatory elements far upstream of the <jats:italic>NF1<\/jats:italic> gene. In an attempt to identify such remotely acting regulatory elements, we reasoned that some of them might reside within DNA sequences that (1) have the potential to interact at distance with the <jats:italic>NF1<\/jats:italic> gene and (2) lie within a histone H3K27ac-enriched region, a characteristic of active enhancers. Combining Hi-C data, obtained by means of the chromosome conformation capture technique, with data on the location and level of histone H3K27ac enrichment upstream of the <jats:italic>NF1<\/jats:italic> gene, we predicted <jats:italic>in silico<\/jats:italic> the presence of two remotely acting regulatory regions, located, respectively, approximately 600 kb and approximately 42 kb upstream of the <jats:italic>NF1<\/jats:italic> gene. These regions were then sequenced in 47 NF1 patients in whom no mutations had been found in either the <jats:italic>NF1<\/jats:italic> or <jats:italic>SPRED1<\/jats:italic> gene regions. Five patients were found to harbour DNA sequence variants in the distal H3K27ac-enriched region. Although these variants are of uncertain pathological significance and still remain to be functionally characterized, this approach promises to be of general utility for the detection of mutations underlying other inherited disorders that may be caused by mutations in remotely acting regulatory elements.<\/jats:p>","DOI":"10.1186\/1479-7364-7-18","type":"journal-article","created":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T18:59:54Z","timestamp":1376593194000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Screening in silico predicted remotely acting NF1gene regulatory elements for mutations in patients with neurofibromatosis type 1"],"prefix":"10.1186","volume":"7","author":[{"given":"Stephen E","family":"Hamby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Reviriego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David N","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meena","family":"Upadhyaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Chuzhanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"49_CR1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/978-3-642-32864-0_15","volume-title":"Neurofibromatosis Type 1: Molecular and Cellular Biology","author":"M Upadhyaya","year":"2012","unstructured":"Upadhyaya M, Chuzhanova N, Cooper DN: The somatic mutational spectrum of the NF1 gene. 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