Table 1.

Molecular Genetic Testing Used in Hereditary Transthyretin (ATTR) Amyloidosis

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
TTR Sequence analysis 3>99% 4, 5
Gene-targeted deletion/duplication analysis 6None reported 7
1.
2.

See Molecular Genetics for information on allelic 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.

The most common pathogenic variant, c.148G>A (p.Val50Met), has been identified in many individuals of different ethnic backgrounds; it is found in large clusters in Portugal, Sweden, and Japan.

5.

The gene has four exons; all pathogenic variants identified to date are in exon 2, 3, or 4.

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.

Since hereditary ATTR amyloidosis occurs through a gain-of-function mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant.

From: Hereditary Transthyretin Amyloidosis

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