{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:39:45Z","timestamp":1789000785491,"version":"build-2803163510"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001631","name":"University College Dublin","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001631","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genet"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital diarrheas and enteropathies (CODEs) constitute a heterogeneous group of individually rare disorders manifesting with infantile-onset chronic diarrhea. Genomic deletions in chromosome 16, encompassing a sequence termed the \u2018intestine-critical region (ICR)\u2019, were recently identified as the cause of an autosomal recessive congenital enteropathy. The regulatory sequence within the ICR is flanked by an unannotated open reading frame termed <jats:italic>PERCC1<\/jats:italic>, which plays a role in enteroendocrine cell (EEC) function. We investigated two unrelated children with idiopathic congenital diarrhea requiring home parenteral nutrition attending the Irish Intestinal Failure Program. Currently 12 and 19-years old, these Irish male patients presented with watery diarrhea and hypernatremic dehydration in infancy. Probands were phenotyped by comprehensive clinical investigations, including endoscopic biopsies and serum gastrin level measurements. Following negative exome sequencing, PCR and Sanger sequencing of the entire coding region and intron boundaries of <jats:italic>PERCC1<\/jats:italic> were performed for each proband and their parents. In both patients, serum gastrin levels were low and failed to increase following a meal challenge. While no deletions involving the ICR were detected, targeted sequencing of the <jats:italic>PERCC1<\/jats:italic> gene revealed a shared homozygous c.390C\u2009&gt;\u2009G stop gain variant. We report clinical and molecular findings in two unrelated patients harboring a shared homozygous variant in <jats:italic>PERCC1<\/jats:italic>, comprising the first description of a point mutation in this gene in association with CODE. That both parenteral nutrition dependent children with unexplained diarrhea at our institution harbored a <jats:italic>PERCC1<\/jats:italic> mutation underscores the importance of its inclusion in exome sequencing interpretation.<\/jats:p>","DOI":"10.1007\/s00439-022-02486-1","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T03:27:10Z","timestamp":1662694030000},"page":"691-696","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nonsense mutation in the novel PERCC1 gene as a genetic cause of congenital diarrhea and enteropathy"],"prefix":"10.1007","volume":"142","author":[{"given":"Dina","family":"Marek-Yagel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Stenke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Pode-Shakked","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Dunne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Crushell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthea","family":"Bryce-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen J.","family":"O\u2019Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvit","family":"Veber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansa","family":"Krishnamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Bourke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"issue":"4","key":"2486_CR1","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1542\/peds.41.4.712","volume":"41","author":"GB Avery","year":"1968","unstructured":"Avery GB, Villavicencio O, Lilly JR, Randolph JG (1968) Intractable diarrhea in early infancy. Pediatrics 41(4):712\u2013722","journal-title":"Pediatrics"},{"issue":"6","key":"2486_CR2","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1097\/MPG.0000000000003049","volume":"72","author":"M Caralli","year":"2021","unstructured":"Caralli M, Roman C, Coste ME, Roquelaure B, Buffat C, Bourgeois P, Badens C, Fabre A (2021) Genetic enteropathies linked to epithelial structural abnormalities and enteroendocrine deficiency: a systematic review. J Pediatr Gastroenterol Nutr 72(6):826\u2013832","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"2","key":"2486_CR3","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3390\/diagnostics11020262","volume":"11","author":"MV Esposito","year":"2021","unstructured":"Esposito MV, Comegna M, Cernera G, Gelzo M, Paparo L, Berni Canani R, Castaldo G (2021) NGS gene panel analysis revealed novel mutations in patients with rare congenital diarrheal disorders. 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J Clin Endocrinol Metab 106(4):1084\u20131090","journal-title":"J Clin Endocrinol Metab"},{"issue":"7763","key":"2486_CR7","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41586-019-1312-2","volume":"571","author":"D Oz-Levi","year":"2019","unstructured":"Oz-Levi D, Olender T, Bar-Joseph I, Zhu Y, Marek-Yagel D, Barozzi I, Osterwalder M, Alkelai A, Ruzzo EK, Han Y, Vos ESM, Reznik-Wolf H, Hartman C, Shamir R, Weiss B, Shapiro R, Pode-Shakked B, Tatarskyy P, Milgrom R, Schvimer M, Barshack I, Imai DM, Coleman-Derr D, Dickel DE, Nord AS, Afzal V, van Bueren KL, Barnes RM, Black BL, Mayhew CN, Kuhar MF, Pitstick A, Tekman M, Stanescu HC, Wells JM, Kleta R, de Laat W, Goldstein DB, Pras E, Visel A, Lancet D, Anikster Y, Pennacchio LA (2019) Noncoding deletions reveal a gene that is critical for intestinal function. 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