title: LGI1 microdeletion in autosomal dominant lateral temporal epilepsy.
abstract: OBJECTIVE
  To characterize clinically and genetically a family with autosomal dominant lateral temporal epilepsy (ADLTE) negative to LGI1 exon sequencing test.
  
  
  METHODS
  All participants were personally interviewed and underwent neurologic examination. Most affected subjects underwent EEG and neuroradiologic examinations (CT/MRI). Available family members were genotyped with the HumanOmni1-Quad v1.0 single nucleotide polymorphism (SNP) array beadchip and copy number variations (CNVs) were analyzed in each subject. LGI1 gene dosage was performed by real-time quantitative PCR (qPCR).
  
  
  RESULTS
  The family had 8 affected members (2 deceased) over 3 generations. All of them showed GTC seizures, with focal onset in 6 and unknown onset in 2. Four patients had focal seizures with auditory features. EEG showed only minor sharp abnormalities in 3 patients and MRI was unremarkable in all the patients examined. Three family members presented major depression and anxiety symptoms. Routine LGI1 exon sequencing revealed no point mutation. High-density SNP array CNV analysis identified a genomic microdeletion about 81 kb in size encompassing the first 4 exons of LGI1 in all available affected members and in 2 nonaffected carriers, which was confirmed by qPCR analysis.
  
  
  CONCLUSIONS
  This is the first microdeletion affecting LGI1 identified in ADLTE. Families with ADLTE in which no point mutations are revealed by direct exon sequencing should be screened for possible genomic deletion mutations by CNV analysis or other appropriate methods. Overall, CNV analysis of multiplex families may be useful for identifying microdeletions in novel disease genes.
authors.affiliation: Porto Conte Ricerche, Alghero, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fanciulli
authors.forename: L
authors.initials: L
authors.lastname: Santulli
authors.forename: L
authors.initials: L
authors.lastname: Errichiello
authors.forename: C
authors.initials: C
authors.lastname: Barozzi
authors.forename: L
authors.initials: L
authors.lastname: Tomasi
authors.forename: L
authors.initials: L
authors.lastname: Rigon
authors.forename: T
authors.initials: T
authors.lastname: Cubeddu
authors.forename: A
authors.initials: A
authors.lastname: de Falco
authors.forename: A
authors.initials: A
authors.lastname: Rampazzo
authors.forename: R
authors.initials: R
authors.lastname: Michelucci
authors.forename: S
authors.initials: S
authors.lastname: Uzzau
authors.forename: S
authors.initials: S
authors.lastname: Striano
authors.forename: F A
authors.initials: FA
authors.lastname: de Falco
authors.forename: P
authors.initials: P
authors.lastname: Striano
authors.forename: C
authors.initials: C
authors.lastname: Nobile
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D001007:Anxiety / Q000150:complications; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000150:complications; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D000078330:Oxcarbazepine; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins; D002220:Carbamazepine; D000078330:Oxcarbazepine