{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:12:21Z","timestamp":1753891941561,"version":"3.41.2"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hirschsprung disease (HSCR) is a heterogeneous genetic disease characterized by the absence of ganglion cells in the intestinal tract. The <jats:italic>REarranged during Transfection (RET)<\/jats:italic> is the most responsible gene for its pathogenesis. RET\u2019s somatic mosaicisms have been reported for HSCR; however, they are still under-recognized. Therefore, we determined the frequency of somatic mutation of <jats:italic>RET<\/jats:italic> rs2435357 in HSCR patients at our institution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed <jats:italic>RET<\/jats:italic> rs2435357 genotyping from 73 HSCR formalin-fixed and paraffin-embedded (FFPE) rectal and 60 non-HSCR controls using the PCR-RFLP method. Subsequently, we compared those frequencies of genotypes for <jats:italic>RET<\/jats:italic> rs2435357 with our previous genotyping data from 93 HSCR blood specimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequencies of genotypes for <jats:italic>RET<\/jats:italic> rs2435357 in HSCR paraffin-embedded rectal were CC 0, CT 11 (15%), and TT 62 (85%), whereas their frequencies in HSCR blood samples were CC 4 (4.3%), CT 22 (23.7%), and TT 67 (72%). Those frequencies differences almost reached a significant level (<jats:italic>p<\/jats:italic> = 0.06). Moreover, the frequency of <jats:italic>RET<\/jats:italic> rs2435357 risk allele (T) was significantly higher in HSCR patients (135\/146, 92.5%) than controls (46\/120, 38.3%) (<jats:italic>p<\/jats:italic> = 3.4 \u00d7 10<jats:sup>\u201322<\/jats:sup>), with an odds ratio of 19.74 (95% confidence interval = 9.65\u201340.41).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study suggests somatic mosaicism in HSCR patients. These findings further imply the complexity of the pathogenesis of HSCR. Moreover, our study confirms the <jats:italic>RET<\/jats:italic> rs2435357 as a significant genetic risk factor for HSCR patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.842820","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T12:48:28Z","timestamp":1646916508000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Is There Any Mosaicism in REarranged During Transfection Variant in Hirschsprung Disease\u2019s Patients?"],"prefix":"10.3389","volume":"10","author":[{"given":"Kristy","family":"Iskandar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Simanjaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taufik","family":"Indrawan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvin Santoso","family":"Kalim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Marcellus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didik Setyo","family":"Heriyanto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Gunadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.ydbio.2013.05.019","article-title":"Contribution of rare and common variants determine complex diseases\u2014Hirschsprung disease as a model.","volume":"382","author":"Alves","year":"2013","journal-title":"Dev Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1056\/NEJMoa1706594","article-title":"Molecular genetic anatomy and 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