title: Autosomal dominant lateral temporal epilepsy (ADLTE): novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras.
abstract: OBJECTIVE
  Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients.
  
  
  METHODS
  Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography.
  
  
  RESULTS
  We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T > C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T > C; p.C286R) in a sporadic patient with auditory seizures.
  
  
  CONCLUSIONS
  We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1, the second so far identified, suggests that LGI1 microrearrangements may not be exceptional.
authors.affiliation: CNR-Neuroscience Institute, Section of Padua, Padova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Dazzo
authors.affiliation: Department of Neurological Sciences, Federico II University, Napoli, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Santulli
authors.affiliation: IRCCS-Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Annio
authors.initials: A
authors.lastname: Posar
authors.affiliation: Department of Neurological Sciences, La Sapienza University, Roma, Italy.
authors.forename: Jinane
authors.initials: J
authors.lastname: Fattouch
authors.affiliation: IRCCS-Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Conti
authors.affiliation: MRC-Holland, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Lodén-van Straaten
authors.affiliation: MRC-Holland, Amsterdam, The Netherlands.
authors.forename: Jona
authors.initials: J
authors.lastname: Mijalkovic
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: De Bortoli
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rosa
authors.affiliation: CRIBI, University of Padova, Padova, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Millino
authors.affiliation: CRIBI, University of Padova, Padova, Italy.
authors.forename: Beniamina
authors.initials: B
authors.lastname: Pacchioni
authors.affiliation: Department of Neurological Sciences, La Sapienza University, Roma, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Bonaventura
authors.affiliation: Department of Neurological Sciences, La Sapienza University, Roma, Italy.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Giallonardo
authors.affiliation: Department of Neurological Sciences, Federico II University, Napoli, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Institute "G. Gaslini", University of Genova, Genova, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: IRCCS-Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Parmeggiani
authors.affiliation: CNR-Neuroscience Institute, Section of Padua, Padova, Italy. Electronic address: nobile@bio.unipd.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Nobile
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D056915:DNA Copy Number Variations; D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005190:Family; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D012893:Sleep Wake Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins
keywords: LGI1; Microdeletion; Mutation; Temporal lobe epilepsy; Visual aura