Table 1.

Summary of Molecular Genetic Testing Used in TARDBP-Related Amyotrophic Lateral Sclerosis

Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method
TARDBPSequence analysis 2Approaches 100% 3
Deletion/duplication analysis 4See footnote 5

See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.


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


Because TARDBP-related ALS is defined by the presence of a pathogenic variant in TARDBP, and because variant types that are not detected by sequence analysis (e.g., exon or whole-gene deletions) have not been reported, the variant detection rate for TARDBP using sequence analysis approaches 100%.


Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


No large deletions or insertions have been reported. Screening for these types of variants has been reported in 714 patients using rt-PCR or multiplexed amplicon quantification (MAQ) [Guerreiro et al 2008, Rutherford et al 2008, Bäumer et al 2009, Benajiba et al 2009, Gijselinck et al 2009]. Since the proposed mechanism that leads to TARDBP-related ALS is gain-of-function of TARDBP, it is unlikely that copy number variants in TARDBP will comprise a significant number of cases.

From: TARDBP-Related Amyotrophic Lateral Sclerosis

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