{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:53:07Z","timestamp":1791611587683,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T00:00:00Z","timestamp":1384992000000},"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\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Genome Quebec"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>Spinal muscular atrophy with progressive myoclonic epilepsy (<jats:styled-content style=\"fixed-case\">SMA\u2010PME<\/jats:styled-content>) is a recently delineated, autosomal recessive condition caused by rare mutations in the N\u2010acylsphingosine amidohydrolase 1 (acid ceramidase) <jats:italic><jats:styled-content style=\"fixed-case\">ASAH1<\/jats:styled-content><\/jats:italic> gene. It is characterized by motor neuron disease followed by progressive myoclonic seizures and eventual death due to respiratory insufficiency. Here we report an adolescent female who presented with atonic and absence seizures and myoclonic jerks and was later diagnosed as having myoclonic\u2010absence seizures. An extensive genetic and metabolic work\u2010up was unable to arrive at a molecular diagnosis. Whole exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) identified two rare, deleterious mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">ASAH1<\/jats:styled-content><\/jats:italic> gene: c.<jats:styled-content style=\"fixed-case\">850G<\/jats:styled-content>&gt;T;p.Gly284X and c.<jats:styled-content style=\"fixed-case\">456A<\/jats:styled-content>&gt;C;p.Lys152Asn. These mutations were confirmed by Sanger sequencing in the patient and her parents. Functional studies in cultured fibroblasts showed that acid ceramidase was reduced in both overall amount and enzymatic activity. Ceramide level was doubled in the patient's fibroblasts as compared to control cells. The results of the <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> and the functional studies prompted an electromyography (<jats:styled-content style=\"fixed-case\">EMG<\/jats:styled-content>) study that showed evidence of motor neuron disease despite only mild proximal muscle weakness. These findings expand the phenotypic spectrum of <jats:styled-content style=\"fixed-case\">SMA\u2010PME<\/jats:styled-content> caused by novel mutations in <jats:italic><jats:styled-content style=\"fixed-case\">ASAH1<\/jats:styled-content><\/jats:italic> and highlight the clinical utility of <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> for rare, intractable forms of epilepsy.<\/jats:p>","DOI":"10.1111\/cge.12307","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T17:43:25Z","timestamp":1382723005000},"page":"558-563","source":"Crossref","is-referenced-by-count":43,"title":["Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy"],"prefix":"10.1111","volume":"86","author":[{"given":"D.A.","family":"Dyment","sequence":"first","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Children's Hospital 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