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- Title
Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11-q13.31.
- Authors
Bisulli, Francesca; Naldi, Ilaria; Baldassari, Sara; Magini, Pamela; Licchetta, Laura; Castegnaro, Giovanni; Fabbri, Margherita; Stipa, Carlotta; Ferrari, Simona; Seri, Marco; Gonçalves Silva, Gilson Edmar; Tinuper, Paolo; Pippucci, Tommaso
- Abstract
Objective To clinically and genetically characterize a large Brazilian family with autosomal dominant partial epilepsy with auditory features ( ADPEAF) not related to leucine-rich, glioma-inactivated 1 ( LGI1) gene. Methods Seventy family members (four married-ins) participating in the study were assessed by a detailed clinical interview and a complete neurologic examination. Genetic mapping was conducted through autosome-wide single nucleotide polymorphism ( SNP) genotyping and subsequent linkage analysis on 16 and haplotype analysis on 25 subjects, respectively. Results The pedigree comprised 15 affected members, of whom 11 were included in the study ( male/ female: 6/5; mean age 39.5 years). All but two ( III:22 and IV:92) had focal seizures with auditory aura followed by secondary generalization in 44.4%. The mean age at onset of epilepsy seizures was 13.7 years. Initial autosome-wide SNP linkage analysis conducted on 12 subjects (8 affected) pointed to a single genomic region on chromosome 19 with a maximum multipoint logarithm of the odds ( LOD) score of 2.60. Further refinement of this region through SNP and microsatellite genotyping on 16 subjects (11 affected) increased the LOD score to 3.41, thereby establishing 19q13.11-q13.31 as a novel ADPEAF locus. Haplotype analysis indicated that the underlying mutation is most likely located in a 9.74 Mb interval between markers D19 S416 and D19 S420. Sequence analysis of the most prominent candidate genes within this critical interval ( SCN1B , LGI4 , KCNK6 , and LRFN1) did not reveal any mutation. Significance This study disclosed a novel ADPEAF locus on chromosome 19q13.11-q13.31, contributing to future identification of a second dominant gene for this epileptic syndrome. A PowerPoint slide summarizing this article is available for download in the Supporting Information section .
- Subjects
GENETICS of epilepsy; SINGLE nucleotide polymorphisms; GENETIC polymorphisms; NEUROLOGIC examination; GENOTYPE-environment interaction
- Publication
Epilepsia (Series 4), 2014, Vol 55, Issue 6, p841
- ISSN
0013-9580
- Publication type
Article
- DOI
10.1111/epi.12560