{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:52:23Z","timestamp":1791183143076,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T00:00:00Z","timestamp":1366934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In relatively small series, autosomal dominant lateral temporal epilepsy (<jats:styled-content style=\"fixed-case\">ADLTE<\/jats:styled-content>) has been associated with leucine\u2010rich, glioma\u2010inactivated 1 (<jats:italic><jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1<\/jats:italic>) mutations in about 50% of the families, this genetic heterogeneity being probably caused by differences in the clinical characteristics of the families. In this article we report the overall clinical and genetic spectrum of<jats:styled-content style=\"fixed-case\">ADLTE<\/jats:styled-content>in Italy with the aim to provide new insight into its nosology and genetic basis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a collaborative study of the Commission of Genetics of the Italian League Against Epilepsy (LICE) encompassing a 10\u2010year period (2000\u20132010), we collected 33<jats:styled-content style=\"fixed-case\">ADLTE<\/jats:styled-content>families, selected on the basis of the following criteria: presence of at least two members concordant for unprovoked partial seizures with prominent auditory and or aphasic symptoms, absence of any known structural brain pathology or etiology, and normal neurologic examination. The clinical, neurophysiologic, and neuroradiologic findings of all patients were analyzed and a genealogic tree was built for each pedigree. The probands'<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>was tested for<jats:italic><jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1<\/jats:italic>mutations by direct sequencing and, if negative, were genotyped with single\u2010nucleotide polymorphism (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>) array to search for disease\u2010linked copy\u2010number variation<jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>. The disease penetrance in mutated and nonmutated families was assessed as a proportion of obligate carriers who were affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>The 33 families included a total of 127 affected individuals (61 male, 66 female, 22 deceased). The age at onset ranged between 2 and 60\u00a0years (mean 18.7\u00a0years). Ninety\u2010one patients (72%) had clear\u2010cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Other symptoms included complex visual hallucinations, vertigo, and d\u00e9j\u00e0 vu. Aphasic seizures, associated or not with auditory features, were observed in 20% of the cases, whereas tonic\u2013clonic seizures occurred in 86% of the overall series. Sudden noises could precipitate the seizures in about 20% of cases. Seizures, which usually occurred at a low frequency, were promptly controlled or markedly improved by antiepileptic treatment in the majority of patients. The interictal electroencephalography (<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>) studies showed the epileptiform temporal abnormalities in 62% of cases, with a slight predominance over the left region. Magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) or computerized tomography (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>) scans were negative.<jats:italic><jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1<\/jats:italic>mutations (missense in nine and a microdeletion in one) were found in only 10 families (30%). The patients belonging to the mutated and not mutated groups did not differ except for penetrance estimate, which was 61.3% and 35% in the two groups, respectively (chi\u2010square, p\u00a0=\u00a00.017). In addition, the disease risk of members of families with mutations in<jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1 was three times higher than that of members of<jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1\u2010negative families (odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>]\u00a02.94, confidence interval [CI] 1.2\u20137.21).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>A large number of<jats:styled-content style=\"fixed-case\">ADLTE<\/jats:styled-content>families has been collected over a 10\u2010year period in Italy, showing a typical and homogeneous phenotype.<jats:italic><jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1<\/jats:italic>mutations have been found in only one third of families, clinically indistinguishable from nonmutated pedigrees. The estimate of penetrance and<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>, however, demonstrates a significantly lower penetrance rate and relative disease risk in non\u2013<jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1\u2010mutated families compared with<jats:styled-content style=\"fixed-case\">LGI<\/jats:styled-content>1\u2010mutated pedigrees, suggesting that a complex inheritance pattern may underlie a proportion of these families.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12194","type":"journal-article","created":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T13:53:01Z","timestamp":1366984381000},"page":"1288-1297","source":"Crossref","is-referenced-by-count":39,"title":["Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without<i><scp>LGI<\/scp>1<\/i>mutations"],"prefix":"10.1111","volume":"54","author":[{"given":"Roberto","family":"Michelucci","sequence":"first","affiliation":[{"name":"Unit of Neurology IRCCS Institute of Neurological Sciences of Bologna Bellaria Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pasini","sequence":"additional","affiliation":[{"name":"Unit of Neurology IRCCS Institute of Neurological Sciences of Bologna Bellaria Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Malacrida","sequence":"additional","affiliation":[{"name":"Department of Biology University of Padua Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Muscular and Neurodegenerative Disease Unit Institute \u201cG. 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