{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:26:37Z","timestamp":1787041597962,"version":"build-2736575974"},"reference-count":10,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>EEFSEC<\/jats:italic>\n                    gene encodes eukaryotic elongation factor selenocysteine\u2013tRNA\u2013specific, an essential component of the selenoprotein biosynthesis machinery required for normal neurodevelopment. Biallelic\n                    <jats:italic>EEFSEC<\/jats:italic>\n                    variants have recently been associated with a rare autosomal recessive neurodevelopmental disorder with variable neurological severity. Here, we describe a Turkish proband carrying the recurrent homozygous\n                    <jats:italic>EEFSEC<\/jats:italic>\n                    (NM_021937.5) variant c.1169A&gt;C; p.Asp390Ala, together with his younger brother, who was identified with the same homozygous variant through familial testing. The proband presented with intellectual disability, delayed motor and expressive language development, mild hypotonia, subtle dysmorphic features, and self\u2010limited early childhood febrile seizures. Compared with previously reported Turkish patients carrying the same variant, his absence of ocular motor involvement, normal neuroimaging, lack of persistent epileptiform abnormalities, and partial developmental gains suggest a relatively milder neurological presentation. The younger brother was initially identified before overt neurological manifestations and subsequently showed delayed expressive language development during early follow\u2010up. This report provides comparative data on the recurrent\n                    <jats:italic>EEFSEC<\/jats:italic>\n                    p.Asp390Ala variant and highlights the value of familial testing, early molecular diagnosis, and longitudinal developmental monitoring in families with confirmed biallelic\n                    <jats:italic>EEFSEC<\/jats:italic>\n                    variants.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70285","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:57:52Z","timestamp":1787039872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genetic Findings in a Turkish Family With the Recurrent Homozygous\n                    <scp>\n                      <i>EEFSEC<\/i>\n                    <\/scp>\n                    p.\n                    <scp>Asp390Ala<\/scp>\n                    Variant"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0669-8230","authenticated-orcid":false,"given":"Kubra","family":"Ates","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital  Bursa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulent","family":"Kara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Kocaeli University Faculty of Medicine  Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"169017","DOI":"10.1016\/j.jmb.2025.169017","article-title":"Understanding the Role of tRNA Modifications in UGA Recoding as Selenocysteine in Eukaryotes","volume":"437","author":"Chavatte L.","year":"2025","journal-title":"Journal of Molecular Biology"},{"issue":"3","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.3390\/ijms25031402","article-title":"Current Understanding of Human Polymorphism in Selenoprotein Genes: A Review of Its Significance as a Risk Biomarker","volume":"25","author":"Ferreira R. R.","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"issue":"3","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.3390\/ijms24032633","article-title":"Biological Activity of Selenium and Its Impact on Human Health","volume":"24","author":"Genchi G.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"issue":"6599","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1126\/science.abg3875","article-title":"Structure of the Mammalian Ribosome as It Decodes the Selenocysteine UGA Codon","volume":"376","author":"Hilal T.","year":"2022","journal-title":"Science"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"102412","DOI":"10.1016\/j.redox.2022.102412","article-title":"Emerging Roles of ER\u2010Resident Selenoproteins in Brain Physiology and Physiopathology","volume":"55","author":"Jehan C.","year":"2022","journal-title":"Redox Biology"},{"issue":"1","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ajhg.2024.12.001","article-title":"EEFSEC Deficiency: A Selenopathy With Early\u2010Onset Neurodegeneration","volume":"112","author":"Laugwitz L.","year":"2025","journal-title":"American Journal of Human Genetics"},{"issue":"1","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s11689-025-09632-6","article-title":"Identifying Compound Heterozygous Variants in the EEFSEC Gene Linked to Progressive Cerebellar Atrophy","volume":"17","author":"Liu Z.","year":"2025","journal-title":"Journal of Neurodevelopmental Disorders"},{"issue":"3","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12011-014-0060-2","article-title":"Selenoproteins in Nervous System Development and Function","volume":"161","author":"Pitts M. W.","year":"2014","journal-title":"Biological Trace Element Research"},{"issue":"5","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards S.","year":"2015","journal-title":"Genetics in Medicine"},{"issue":"11","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1016\/j.bbagen.2018.03.018","article-title":"On Elongation Factor eEFSec, Its Role and Mechanism During Selenium Incorporation Into Nascent Selenoproteins","volume":"1862","author":"Simonovi\u0107 M.","year":"2018","journal-title":"Biochimica et Biophysica Acta (BBA)\u2010General Subjects"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70285","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:57:53Z","timestamp":1787039873000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":10,"alternative-id":["10.1002\/ajmg.a.70285"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70285","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"2026-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70285"}}