{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:45:47Z","timestamp":1764996347530,"version":"3.46.0"},"reference-count":30,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The\n                    <jats:italic>RET<\/jats:italic>\n                    gene encodes a tyrosine kinase receptor involved in different human neurocristopathies, such as specific neuroendocrine tumours and Hirschsprung disease (HSCR). Gene expression is developmentally regulated and the\n                    <jats:italic>RET<\/jats:italic>\n                    transcript is undetectable in most adult cells, including lymphocytes. The impossibility of performing functional studies on\n                    <jats:italic>RET<\/jats:italic>\n                    mRNA has to date limited the detection and characterisation of an indefinite proportion of gene anomalies that cannot be identified by conventional DNA genomic screening in HSCR cases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aims:<\/jats:bold>\n                    Development of a protocol suitable to activate\n                    <jats:italic>RET<\/jats:italic>\n                    expression in\n                    <jats:italic>RET<\/jats:italic>\n                    negative cell lines and therefore to investigate directly\n                    <jats:italic>RET<\/jats:italic>\n                    mRNA, extending the conventional gene mutation analysis to detection of splicing anomalies and impaired expression of the\n                    <jats:italic>RET<\/jats:italic>\n                    gene.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The effect of sodium butyrate (NaB), a histone deacetylase inhibitor, on rescuing\n                    <jats:italic>RET<\/jats:italic>\n                    expression was tested by one round of reverse transcription- polymerase chain reaction from total RNA of treated lymphoblasts from both HSCR patients and control individuals.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Analysis of\n                    <jats:italic>RET<\/jats:italic>\n                    expression was possible by NaB treatment of\n                    <jats:italic>RET<\/jats:italic>\n                    negative cells, such as lymphoblasts. This treatment allowed us to detect impaired\n                    <jats:italic>RET<\/jats:italic>\n                    expression as well as a splicing defect in two HSCR patients previously believed to be devoid of any gene abnormality.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The full application of the proposed protocol in most of the unexplained HSCR cases will allow us to establish the precise role of\n                    <jats:italic>RET<\/jats:italic>\n                    not only in causing but also in predisposing to HSCR pathogenesis.\n                  <\/jats:p>","DOI":"10.1136\/gut.52.8.1154","type":"journal-article","created":{"date-parts":[[2003,7,15]],"date-time":"2003-07-15T15:15:57Z","timestamp":1058282157000},"page":"1154-1158","source":"Crossref","is-referenced-by-count":16,"title":["Rescue of human\n                    <i>RET<\/i>\n                    gene expression by sodium butyrate: a novel powerful tool for molecular studies in Hirschsprung disease"],"prefix":"10.1136","volume":"52","author":[{"given":"P","family":"Griseri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Patrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Puppo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Ravazzolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Ceccherini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2003,7,15]]},"reference":[{"key":"2025120520225979000_52.8.1154.1","first-page":"80","volume":"17","year":"2001","journal-title":"Trends Genet"},{"key":"2025120520225979000_52.8.1154.2","first-page":"229","volume":"54","year":"1998","journal-title":"Recent Results Cancer Res"},{"key":"2025120520225979000_52.8.1154.3","unstructured":"Chakravarti A, Lyonnet S. 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