Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11–q13.31

Abstract

SUMMARYObjective: 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 D19S416 and D19S420. 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.

Copy number variants associated with epilepsy from gene expression microarrays

“…Of note, this chromosome region was also regarded as a risk region for epilepsy [23], harboring dominant genes for epileptic syndrome [14]. Our results confirmed the results of previous studies, that 19q13.11 shows promise as an epilepsy-associated region.…”

“…Over representation of the genes in this region were also found in several cellular function and maintenance categories, including molecular transport, small molecule biochemistry, carbohydrate metabolism and cell cycle. Another region, 19q13.11, was recently considered as a susceptible region related to autosomal dominant partial epilepsy with auditory features [14]. This region harbors genes that relate to hereditary disorders and neurological disease.…”

Molecular typing of familial temporal lobe epilepsy

“…However, the molecular functions of these genes were discrepant, indicating that the mechanism of LTLE was complicated. Notably, some candidate loci were also gradually being recognized, such as the Chr 9q13.11–q13.31 Locus (not mentioned above), which was related to familial LTLE with a higher frequency of febrile seizures and migraine and a lower recurrence of focal to bilateral seizures than ETL1, ETL7 and ETL10[ 58 ].…”

MICAL1 Monooxygenase in Autosomal Dominant Lateral Temporal Epilepsy: Role in Cytoskeletal Regulation and Relation to Cancer

“…Isolated genetic case reports have suggested that unknown mutant genes at various chromosomal loci are linked to ADLTE-like symptoms and seizures [26,27]. An estimated 50% of ADLTE cases could be due to mutations of these uncharacterized genes [7].…”