Table 1.

Molecular Genetic Testing Used in Autosomal Dominant Epilepsy with Auditory Features

Gene 1, 2Proportion of ADEAF Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3in Gene Identified by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
LGI1 ~30% 695%5% 7
MICAL1 ~7% 8~95%-100%None reported to date
RELN ~17%-18% 6~99% 9~1% 10
Unknown 11~50%NA
1.

Genes are listed in alphabetic order.

2.

See Table A. Genes and Databases for chromosome locus and protein.

3.

See Molecular Genetics for information on variants detected in these genes.

4.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

6.
7.

Several partial and total gene deletions involving LGI1 have been identified in families with ADEAF in which exome sequencing did not reveal any pathogenic sequencing alterations [Fanciulli et al 2012, Magini et al 2014, Manna et al 2014, Dazzo et al 2015b, Monlong et al 2018, Coppola et al 2019, Truty et al 2019]

8.
9.
10.
11.

A locus on 19q13.11-q13.31 likely to contain a gene associated with ADEAF was identified in a large Brazilian family [Bisulli et al 2014]. In 21 families with ADEAF, 12 rare copy number variants (CNVs) were identified by genome-wide SNP microarray analysis that segregated with ADEAF in single families, including rare microdeletions within or near RBFOX1 and NRXN1, and a microduplication in the proximal region of chromosome 1q21.1 where duplications have been associated with various neurodevelopmental disorders and epilepsy [Fanciulli et al 2014]. Deletions/duplications at these loci confer susceptibility to other forms of genetic epilepsy syndromes.

From: Autosomal Dominant Epilepsy with Auditory Features

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