{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:55:47Z","timestamp":1779378947273,"version":"3.53.1"},"reference-count":43,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>We describe a case of an infant presenting with intractable diarrhea who subsequently developed dilated cardiomyopathy, for whom a diagnosis was not initially achieved despite extensive clinical testing, including panel-based genetic testing. Research-based whole-genome sequences of the proband and both parents were analyzed by the SAVANNA pipeline, a variant prioritization strategy integrating features of variants, genes, and phenotypes, which was implemented using publicly available tools. Although the intestinal morphological abnormalities characteristic of congenital tufting enteropathy (CTE) were not observed in the initial clinical gastrointestinal tract biopsies of the proband, an intronic variant, <jats:italic>EPCAM<\/jats:italic> c.556-14A&gt;G, previously identified as pathogenic for CTE, was found in the homozygous state. A newborn cousin of the proband also presenting with intractable diarrhea was found to carry the same homozygous <jats:italic>EPCAM<\/jats:italic> variant, and clinical testing revealed intestinal tufting and loss of EPCAM staining. This variant, however, was considered nonexplanatory for the proband's dilated cardiomyopathy, which could be a sequela of the child's condition and\/or related to other genetic variants, which include de novo mutations in the genes <jats:italic>NEDD4L<\/jats:italic> and <jats:italic>GSK3A<\/jats:italic> and a maternally inherited <jats:italic>SCN5A<\/jats:italic> variant. This study illustrates three ways in which genomic sequencing can aid in the diagnosis of clinically challenging patients: differential diagnosis despite atypical clinical presentation, distinguishing the possibilities of a syndromic condition versus multiple conditions, and generating hypotheses for novel contributory genes.<\/jats:p>","DOI":"10.1101\/mcs.a002055","type":"journal-article","created":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T01:00:33Z","timestamp":1499907633000},"page":"a002055","source":"Crossref","is-referenced-by-count":15,"title":["Genomic analysis of an infant with intractable diarrhea and dilated cardiomyopathy"],"prefix":"10.1101","volume":"3","author":[{"given":"Dale L.","family":"Bodian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Vilboux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchitra K.","family":"Hourigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie L.","family":"Jenevein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haresh","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen C.","family":"Kent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Khromykh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie S.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2017,7,12]]},"reference":[{"key":"2021112506132862000_3.6.a002055.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231619298"},{"key":"2021112506132862000_3.6.a002055.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"2021112506132862000_3.6.a002055.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072047"},{"key":"2021112506132862000_3.6.a002055.4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.2.573"},{"key":"2021112506132862000_3.6.a002055.5","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/mgg3.107","article-title":"Diagnosis of an imprinted-gene syndrome by a novel bioinformatics analysis of whole-genome sequences from a family trio","volume":"2","year":"2014","journal-title":"Mol Genet Genomic Med"},{"key":"2021112506132862000_3.6.a002055.6","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.111"},{"key":"2021112506132862000_3.6.a002055.7","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/ng.3676","article-title":"Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia","volume":"48","year":"2016","journal-title":"Nat Genet"},{"key":"2021112506132862000_3.6.a002055.8"},{"key":"2021112506132862000_3.6.a002055.9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12519-015-0070-y","article-title":"Genetic analysis of Italian patients with congenital tufting enteropathy","volume":"12","year":"2016","journal-title":"World J Pediatr"},{"key":"2021112506132862000_3.6.a002055.10","unstructured":"Garrison E , Marth G . 2012. 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