{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:33:20Z","timestamp":1780407200174,"version":"3.54.1"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2011-02347381"],"award-info":[{"award-number":["GR-2011-02347381"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hirschsprung (HSCR) Associated Enterocolitis (HAEC) is a common life-threatening complication in HSCR. HAEC is suggested to be due to a loss of gut homeostasis caused by impairment of immune system, barrier defense, and microbiome, likely related to genetic causes. No gene has been claimed to contribute to HAEC occurrence, yet. Genetic investigation of HAEC by Whole-Exome Sequencing (WES) on 24 HSCR patients affected (HAEC) or not affected (HSCR-only) by enterocolitis and replication of results on a larger panel of patients allowed the identification of the HAEC susceptibility variant p.H187Q in the Oncostatin-M receptor (OSMR) gene (14.6% in HAEC and 5.1% in HSCR-only, p = 0.0024). Proteomic analysis on the lymphoblastoid cell lines from one HAEC patient homozygote for this variant and one HAEC patient not carrying the variant revealed two well distinct clusters of proteins significantly up or downregulated upon OSM stimulation. A marked enrichment in immune response pathways (q &lt; 0.0001) was shown in the HAEC H187 cell line, while proteins upregulated in the HAEC Q187 lymphoblasts sustained pathways likely involved in pathogen infection and inflammation. In conclusion, OSMR p.H187Q is an HAEC susceptibility variant and perturbates the downstream signaling cascade necessary for the gut immune response and homeostasis maintenance.<\/jats:p>","DOI":"10.3390\/ijms22083831","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T11:31:59Z","timestamp":1617795119000},"page":"3831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The OSMR Gene Is Involved in Hirschsprung Associated Enterocolitis Susceptibility through an Altered Downstream Signaling"],"prefix":"10.3390","volume":"22","author":[{"given":"Tiziana","family":"Bachetti","sequence":"first","affiliation":[{"name":"Laboratory of Developmental Neurobiology, Dipartimento di Scienze della Terra dell\u2019Ambiente e della Vita (DISTAV), Universit\u00e0 di Genova, Viale Benedetto XV, 5, 16132 Genova, Italy"},{"name":"UOSD Laboratorio di Genetica e Genomica delle Malattie Rare, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini, 5, 16148 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-9397","authenticated-orcid":false,"given":"Francesca","family":"Rosamilia","sequence":"additional","affiliation":[{"name":"Health Science Department (DISSAL), Biostatistics Unit, Universit\u00e0 di Genova, Via Pastore 1, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5289-4219","authenticated-orcid":false,"given":"Martina","family":"Bartolucci","sequence":"additional","affiliation":[{"name":"Core Facilities-Clinical Proteomics and Metabolomics, IRCCS, Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Santamaria","sequence":"additional","affiliation":[{"name":"UOSD Laboratorio di Genetica e Genomica delle Malattie Rare, IRCCS Istituto Giannina 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di Fisiopatologia dell\u2019 Uremia, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Obino","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Neurobiology, Dipartimento di Scienze della Terra dell\u2019Ambiente e della Vita (DISTAV), Universit\u00e0 di Genova, Viale Benedetto XV, 5, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Avanzini","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Unit, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Mavilio","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, University of Milan, Via Manzoni 113, 20089 Milan, Italy"},{"name":"Laboratory of Clinical and 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