{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:08:57Z","timestamp":1790730537578,"version":"4.1.0"},"reference-count":31,"publisher":"Cold Spring Harbor Laboratory","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>Recent evidence has implicated <jats:italic>EFL1<\/jats:italic> in a phenotype overlapping Shwachman\u2013Diamond syndrome (SDS), with the functional interplay between <jats:italic>EFL1<\/jats:italic> and the previously known causative gene <jats:italic>SBDS<\/jats:italic> accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the <jats:italic>EFL1<\/jats:italic> gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in <jats:italic>EFL1<\/jats:italic> on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with <jats:italic>EFL1<\/jats:italic> variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in <jats:italic>EFL1<\/jats:italic> appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of <jats:italic>EFL1<\/jats:italic> being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent.<\/jats:p>","DOI":"10.1101\/mcs.a003046","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T18:15:41Z","timestamp":1530641741000},"page":"a003046","source":"Crossref","is-referenced-by-count":38,"title":["Further evidence for the involvement of <i>EFL1<\/i> in a Shwachman\u2013Diamond-like syndrome and expansion of the phenotypic features"],"prefix":"10.1101","volume":"4","author":[{"given":"Queenie K.-G.","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Cope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Spillmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Stong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Hui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie T.","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Rothman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan W.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald P.","family":"Frush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph S.","family":"Lachman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Bacino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie J.","family":"Bonner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad M.","family":"McCall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avani A.","family":"Pendse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Walley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Shashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren D.M.","family":"Pena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2018,7,3]]},"reference":[{"key":"2021112506161610000_4.5.a003046.1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"2021112506161610000_4.5.a003046.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.12.143"},{"key":"2021112506161610000_4.5.a003046.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1964.tb07237.x"},{"key":"2021112506161610000_4.5.a003046.4","doi-asserted-by":"publisher","DOI":"10.1136\/adc.42.222.147"},{"key":"2021112506161610000_4.5.a003046.5","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.1172\/JCI92876","article-title":"Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman\u2013Diamond-like features","volume":"127","year":"2017","journal-title":"J Clin Invest"},{"key":"2021112506161610000_4.5.a003046.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1001025"},{"key":"2021112506161610000_4.5.a003046.7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-735431"},{"key":"2021112506161610000_4.5.a003046.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06349.x"},{"key":"2021112506161610000_4.5.a003046.9","doi-asserted-by":"publisher","DOI":"10.1101\/gad.623011"},{"key":"2021112506161610000_4.5.a003046.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.626275"},{"key":"2021112506161610000_4.5.a003046.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(99)70332-X"},{"key":"2021112506161610000_4.5.a003046.12","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jpeds.2009.09.026","article-title":"The behavioral phenotype of school-age children with Shwachman Diamond syndrome indicates neurocognitive dysfunction with loss of Shwachman\u2013Bodian\u2013Diamond syndrome gene function","volume":"156","year":"2010","journal-title":"J Pediatr"},{"key":"2021112506161610000_4.5.a003046.13","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"2021112506161610000_4.5.a003046.14","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"2021112506161610000_4.5.a003046.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"2021112506161610000_4.5.a003046.16","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1007\/s00247-014-3231-6","article-title":"Shwachman\u2013Bodian\u2013Diamond syndrome: metaphyseal chondrodysplasia in children with pancreatic insufficiency and neutropenia","volume":"45","year":"2015","journal-title":"Pediatr Radiol"},{"key":"2021112506161610000_4.5.a003046.17","doi-asserted-by":"publisher","DOI":"10.1038\/ng1994"},{"key":"2021112506161610000_4.5.a003046.18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.038349"},{"key":"2021112506161610000_4.5.a003046.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.11.039"},{"key":"2021112506161610000_4.5.a003046.20","first-page":"7","article-title":"Ribosomopathies: mechanisms of disease","volume":"7","year":"2014","journal-title":"Clin Med Insights Blood Disord"},{"key":"2021112506161610000_4.5.a003046.21","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2021112506161610000_4.5.a003046.22","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"2021112506161610000_4.5.a003046.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(64)80150-5"},{"key":"2021112506161610000_4.5.a003046.24","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104366"},{"key":"2021112506161610000_4.5.a003046.25","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ajhg.2017.04.015","article-title":"Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the Clinical Genome Resource","volume":"100","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2021112506161610000_4.5.a003046.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.06.047"},{"key":"2021112506161610000_4.5.a003046.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.05.002"},{"key":"2021112506161610000_4.5.a003046.28","first-page":"109","article-title":"Molecular basis of the human ribosomopathy Shwachman\u2013Diamond syndrome","volume":"67","year":"2017","journal-title":"Adv Biol Regul"},{"key":"2021112506161610000_4.5.a003046.29","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/gim.2016.88","article-title":"Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers","volume":"19","year":"2017","journal-title":"Genet Med"},{"key":"2021112506161610000_4.5.a003046.30","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062708-134043"},{"key":"2021112506161610000_4.5.a003046.31","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.191"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a003046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T14:16:37Z","timestamp":1637849797000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a003046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,3]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,10,1]]},"published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1101\/mcs.a003046"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a003046","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,3]]}}}