Table 2.

Molecular Genetic Testing Used in Alexander Disease

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
GFAP Sequence analysis 398% 4
Deletion/duplication analysis 5One reported 6
1.

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

2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or 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.

4.

Based on a summary of prior published reports in which 293 of 299 (98%) individuals tested had a GFAP pathogenic variant. Of note, the numerator and denominator include ten asymptomatic individuals who had a pathogenic GFAP variant (see Table 3 [pdf]).

5.

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

6.

Deletion of exon 5, an in-frame exon, has been reported [Green et al 2018].

From: Alexander Disease

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