Table 1.

Molecular Genetic Testing Used in Hereditary Folate Malabsorption

Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
SLC46A1 Sequence analysis 3100% 4, 5
Gene-targeted deletion/duplication analysis 6See footnote 7.
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 not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

5.

One variant found in several individuals of Japanese ancestry was a single-nucleotide deep intron 3 variant that generated a cryptic splice donor site resulting in a 168-bp insertion [Kishimoto et al 2014, Tozawa et al 2019]. Sequencing methodologies that can detect splice donor and acceptor variants should be considered.

6.

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.

7.

To date, large intragenic SLC46A1 deletions and duplications have not been reported.

From: Hereditary Folate Malabsorption

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