{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:13:21Z","timestamp":1790633601761,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1Fi2GM123961"],"award-info":[{"award-number":["1Fi2GM123961"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Rare pathogenic\n                    <jats:italic>EIF2S3<\/jats:italic>\n                    missense and terminal deletion variants cause the X\u2010linked intellectual disability (ID) syndrome MEHMO, or a milder phenotype including pancreatic dysfunction and hypopituitarism. We present two unrelated male patients who carry novel\n                    <jats:italic>EIF2S3<\/jats:italic>\n                    pathogenic missense variants (p.(Thr144Ile) and p.(Ile159Leu)) thereby broadening the limited genetic spectrum and underscoring clinically variable expressivity of MEHMO. While the affected male with p.(Thr144Ile) presented with severe motor delay, severe microcephaly, moderate ID, epileptic seizures responsive to treatments, hypogenitalism, central obesity, facial features, and diabetes, the affected male with p.(Ile159Leu) presented with moderate ID, mild motor delay, microcephaly, epileptic seizures resistant to treatment, central obesity, and mild facial features. Both variants are located in the highly conserved guanine nucleotide binding domain of the\n                    <jats:italic>EIF2S3<\/jats:italic>\n                    encoded eIF2\u03b3 subunit of the heterotrimeric translation initiation factor 2 (eIF2) complex. Further, we investigated both variants in a structural model and in yeast. The reduced growth rates and lowered fidelity of translation with increased initiation at non\u2010AUG codons observed for both mutants in these studies strongly support pathogenicity of the variants.\n                  <\/jats:p>","DOI":"10.1111\/cge.13831","type":"journal-article","created":{"date-parts":[[2020,8,16]],"date-time":"2020-08-16T04:20:03Z","timestamp":1597551603000},"page":"507-514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Novel pathogenic\n                    <scp>\n                      <i>EIF2S3<\/i>\n                    <\/scp>\n                    missense variants causing clinically variable\n                    <scp>MEHMO<\/scp>\n                    syndrome with impaired\n                    <scp>eIF2\u03b3<\/scp>\n                    translational function, and literature review"],"prefix":"10.1111","volume":"98","author":[{"given":"Urania","family":"Kotzaeridou","sequence":"first","affiliation":[{"name":"Division of Child Neurology and Inherited Metabolic Diseases, Centre for Paediatrics and Adolescent Medicine University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara K.","family":"Young\u2010Baird","sequence":"additional","affiliation":[{"name":"<i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development NIH  Bethesda Maryland USA"},{"name":"National Institute of General Medical Sciences NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Suckow","sequence":"additional","affiliation":[{"name":"Research Group Development and Disease Max Planck Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis G.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"<i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-8823","authenticated-orcid":false,"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University M\u00fcnchen  Munich Germany"},{"name":"Institute of Human Genetics, Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"},{"name":"Institute for Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Harting","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine","family":"Christ","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Inherited Metabolic Diseases, Centre for Paediatrics and Adolescent Medicine University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Strom","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Dever","sequence":"additional","affiliation":[{"name":"<i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6898-3259","authenticated-orcid":false,"given":"Vera 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