Familial Transthyretin Amyloidosis (TTR) Sequencing

Interpretive Data: Background Information for Familial Transthyretin Amyloidosis (TTR) Sequencing:
Characteristics: Familial Transthyretin Amyloidosis  is caused by pathogenic variants of the TTR gene resulting in abnormal amyloid accumulation in various tissues and is generally categorized into three phenotypes:  1) familial amyloid polyneuropathy, a slowly progressive sensorimotor and autonomic neuropathy; 2) familial amyloid cardiomyopathy, a restrictive cardiomyopathy with cardiomegaly, conduction block, angina, congestive heart failure and aortic dissection/dilatation; and 3) leptomeningeal amyloidosis, primarily affecting the CNS, causing dementia, visual impairment, seizures, ataxia, psychosis, hemorrhage, and hydrocephalus. TTR variants can also be associated with benign familial euthyroid hyperthyroxinemia.
Incidence: 1 in 568 individuals from Northern Portugal; 1 in 100,000 individuals of Northern European ancestry.
Inheritance: Autosomal dominant.
Penetrance: Incomplete.
Cause: Pathogenic TTR gene variants.
Clinical Sensitivity: 99 percent for Familial TTR Amyloidosis.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the TTR gene.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants, deep intronic variants and large deletions/duplications in TTR will not be detected.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.