Table 1.

Molecular Genetic Testing Used in Arylsulfatase A Deficiency

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
ARSA Sequence analysis 390%-95% 4
Gene-targeted deletion/duplication analysis 5<1% 6
1.
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 missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are undetected. For issues to consider in the interpretation of sequence analysis results, click here [Karczewski et al 2020].

4.

This test method also detects the ARSA pseudodeficiency alleles (termed ARSA-PD), common variants that result in lower-than-average arylsulfatase A enzyme activity but do not cause MLD either when biallelic or compound heterozygous with an ARSA-MLD allele.

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.

Complete deletion of ARSA associated with MLD has been reported [Eng et al 2004, Bisgaard et al 2009].

From: Arylsulfatase A Deficiency

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