{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:28:13Z","timestamp":1780338493878,"version":"3.54.1"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005187","name":"NRC","doi-asserted-by":"publisher","award":["11010167"],"award-info":[{"award-number":["11010167"]}],"id":[{"id":"10.13039\/100005187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005187","name":"NRC","doi-asserted-by":"publisher","award":["12060178"],"award-info":[{"award-number":["12060178"]}],"id":[{"id":"10.13039\/100005187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study presents 46 patients from 23 unrelated Egyptian families with\n                    <jats:italic>ALS2<\/jats:italic>\n                    \u2010related disorders without evidence of lower motor neuron involvement. Age at onset ranged from 10\u2009months to 2.5\u2009years, featuring progressive upper motor neuron signs. Detailed clinical phenotypes demonstrated inter\u2010 and intrafamilial variability. We identified 16 homozygous disease\u2010causing\n                    <jats:italic>ALS2<\/jats:italic>\n                    variants; sorted as splice\u2010site, missense, frameshift, nonsense and in\u2010frame in eight, seven, four, three, and one families, respectively. Seven of these variants were novel, expanding the mutational spectrum of the\n                    <jats:italic>ALS2<\/jats:italic>\n                    gene. As expected, clinical severity was positively correlated with disease onset (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004). This work provides clinical and molecular profiles of a large single ethnic cohort of patients with\n                    <jats:italic>ALS2<\/jats:italic>\n                    mutations, and suggests that infantile ascending hereditary spastic paralysis (IAHSP) and juvenile primary lateral sclerosis (JPLS) are belonged to one entity with no phenotype\u2013genotype correlation.\n                  <\/jats:p>","DOI":"10.1111\/cge.14338","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:20:14Z","timestamp":1681431614000},"page":"238-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical and molecular spectrum of a large Egyptian cohort with\n                    <scp>\n                      <i>ALS2<\/i>\n                    <\/scp>\n                    \u2010related disorders of infantile\u2010onset of clinical continuum\n                    <scp>IAHSP<\/scp>\n                    \/\n                    <scp>JPLS<\/scp>"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-0002","authenticated-orcid":false,"given":"Maha S.","family":"Zaki","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4728-9089","authenticated-orcid":false,"given":"Wessam E.","family":"Sharaf\u2010Eldin","sequence":"additional","affiliation":[{"name":"Department of Medical Molecular Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Rafat","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnaa M.","family":"Elbendary","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Kamel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Elkhateeb","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Cairo University  Cairo Egypt"},{"name":"Department of Clinical Genetics Cambridge University Hospitals  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2289-8950","authenticated-orcid":false,"given":"Mahmoud M.","family":"Noureldeen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Abdeltawab","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahim A.","family":"Sadek","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona L.","family":"Essawi","sequence":"additional","affiliation":[{"name":"Department of Medical Molecular Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-0147","authenticated-orcid":false,"given":"Mohamed S.","family":"Abdel\u2010Hamid","sequence":"additional","affiliation":[{"name":"Department of Medical Molecular Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Holuden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3899-2821","authenticated-orcid":false,"given":"Mahmoud Y.","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G.","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California  San Diego La Jolla USA"},{"name":"Rady Children's Hospital Rady Children's Institute for Genomic Medicine  San Diego La Jolla USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"ALS2\u2010Related Disorder","author":"Orrell 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