{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:49:18Z","timestamp":1790419758228,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Agency for Science, Technology and Research (A*STAR), Singapore","award":["Genetic Orphan Diseases Adopted: Fostering Innovation Therapy (GODAFIT) - Strategic Positioning Fund SPF2012\/005"],"award-info":[{"award-number":["Genetic Orphan Diseases Adopted: Fostering Innovation Therapy (GODAFIT) - Strategic Positioning Fund SPF2012\/005"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Shwachman\u2013Diamond syndrome (SDS) is a rare multisystem ribosomal biogenesis disorder characterized by exocrine pancreatic insufficiency, hematologic abnormalities and bony abnormalities. About 90% of patients have biallelic mutations in <jats:italic>SBDS<\/jats:italic> gene. Three additional genes\u2014<jats:italic>EFL1, DNAJC21 and SRP54<\/jats:italic> have been reported in association with a SDS phenotype. However, the cause remains unknown for ~10% of patients. Herein, we report a 6\u2010year\u2010old Chinese boy, who presented in the neonatal period with pancytopenia, liver transaminitis with hepatosplenomegaly and developmental delay, and subsequently developed pancreatic insufficiency complicated by malabsorption and poor growth. Exome sequencing identified a novel <jats:italic>de novo<\/jats:italic> heterozygous variant in <jats:italic>EIF6<\/jats:italic> (c.182G&gt;T, p.Arg61Leu). EIF6 protein inhibits ribosomal maturation and is removed in the late steps of ribosomal maturation by SBDS and EFL1 protein. Given the interaction of <jats:italic>EIF6<\/jats:italic> with <jats:italic>SBDS<\/jats:italic> and <jats:italic>EFL1<\/jats:italic>, we postulate heterozygous variants in <jats:italic>EIF6<\/jats:italic> as a novel cause of Shwachman\u2013Diamond\u2010like phenotype. We compared the phenotype of our patient with those in patients with mutation in <jats:italic>SBDS<\/jats:italic>, <jats:italic>EFL1<\/jats:italic>, <jats:italic>DNAJC21<\/jats:italic>, and <jats:italic>SRP54<\/jats:italic> genes to support this association. Identification of more cases of this novel phenotype would strengthen the association with the genetic etiology.<\/jats:p>","DOI":"10.1002\/ajmg.a.61758","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T08:28:41Z","timestamp":1594628921000},"page":"2010-2020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Heterozygous missense variant in <scp><i>EIF6<\/i><\/scp> gene: A novel form of <scp>Shwachman\u2013Diamond<\/scp> syndrome?"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4514-6869","authenticated-orcid":false,"given":"Ai Ling","family":"Koh","sequence":"first","affiliation":[{"name":"Department of Paediatrics KK Women's and Children's Hospital, Singapore  Singapore Singapore"},{"name":"Paediatric Academic Clinical Programme Duke\u2010NUS Medical School  Singapore 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