{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:57:27Z","timestamp":1781153847090,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T00:00:00Z","timestamp":1509148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>We have ascertained two families affected with familial amyotrophic lateral sclerosis (ALS) in which they both carry a hexanucleotide repeat expansion in the <jats:italic>C9orf72<\/jats:italic> gene, specifically in individuals who also presented with frontotemporal dementia (FTD) or behavioral variant FTD (bvFTD). While some reports attribute this phenotypic heterogeneity to the <jats:italic>C9orf72<\/jats:italic> expansion alone, we screened for additional genetic variation in known ALS\u2010FTD genes that may also contribute to or modify the phenotypes. We performed genetic testing consisting of <jats:italic>C9orf72<\/jats:italic> hexanucleotide expansion, <jats:italic>ATXN2<\/jats:italic> polyglutamine (polyQ) expansion, and targeted next generation sequencing using the ONDRISeq, a gene panel consisting of 80 genes known to be associated with neurodegenerative diseases such as ALS, FTD, Alzheimer's disease, Parkinson's disease, and vascular cognitive impairment. In addition to the <jats:italic>C9orf72<\/jats:italic> expansion, we observed an <jats:italic>ATXN2<\/jats:italic> polyQ intermediate length expansion, and <jats:italic>OPTN<\/jats:italic> p.Met468Arg in patients who exhibited ALS and FTD or bvFTD. We conclude that the <jats:italic>C9orf72<\/jats:italic> expansion likely explains much of the ALS\u2010FTD phenotype; however, inheritance of these additional variants likely modifies the disease course and may provide further evidence for biologically relevant oligogenic inheritance in ALS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32606","type":"journal-article","created":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T11:26:37Z","timestamp":1509189997000},"page":"75-85","source":"Crossref","is-referenced-by-count":20,"title":["OPTN p.Met468Arg and ATXN2 intermediate length polyQ extension in families with C9orf72 mediated amyotrophic lateral sclerosis and frontotemporal dementia"],"prefix":"10.1002","volume":"177","author":[{"given":"Sali M. 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