Journal: Journal of Clinical Medicine

Article Title: Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis †

doi: 10.3390/jcm14196821

Figure Lengend Snippet: Variants identified in the TTR gene in ( a ) GeneAct ® and ( b ) Alnylam Act ® . 1 Other variants were D74H (p.D94H), T60A (p.T80A), V71A (p.V91A) (all n = 2), A25S (p.A45S), R103H (p.R123H), p.R5H, E89Q (p.E109Q), E89K (p.E109K), E7* (p.E27*), E54Q (p.E74Q), E61G (p.E81G), G67V (p.G87V), H31N (p.H51N), S100T (p.S120T), and S77F (p.S97F) (all n = 1). 2 Includes 5 variants of uncertain significance that were identified in 6 symptomatic participants but were excluded from the calculation of diagnostic yield. 3 Includes 4 participants with 2 variants: V122I (p.V142I) and R103H (p.R123H), V122I (p.V142I) and I107V (p.I127V), V122I (p.V142I) and I68L (p.I88L), and V122I (p.V142I) and T60I (p.T80I) (all n = 1). 4 Includes L58H (p.L78H) ( n = 63), P64L (p.P84L) ( n = 61), I107V (p.I127V) ( n = 36), I68L (p.I88L) ( n = 29), S77T (p.S97T) ( n = 25), and P24S (p.P44S) ( n = 21) (see for the full list of other variants identified). * indicates a stop codon. Percentages may not add up to 100 due to rounding.

Article Snippet: Individuals eligible for testing in the Alnylam Act ® program were ≥18 years of age with ≥1 ATTRv high index of suspicion indicator that included family history of ATTRv amyloidosis; positive imaging consistent with amyloid (technetium, cardiac magnetic resonance, strain echo); or positive biopsy for TTR amyloid; or ≥2 ATTRv index of suspicion indicators that included sensory and/or motor neuropathy (e.g., neuropathic pain, altered sensation, numbness and tingling, muscle weakness, impaired balance, difficulty walking, carpal tunnel syndrome-associated neuropathy, electromyography/nerve conduction study abnormalities); autonomic dysfunction (e.g., nausea and vomiting, changes in gastrointestinal motility, orthostatic hypotension, sexual dysfunction, bladder dysfunction); heart disease (e.g., cardiomyopathy, restrictive physiology, hypertrophy, arrhythmias, conduction abnormalities, heart failure, abnormal cardiac imaging); musculoskeletal indicators (history of carpal tunnel syndrome, back pain/lumbar spinal stenosis, rotator cuff injury); renal abnormalities (e.g., renal insufficiency and/or proteinuria); and ocular changes (e.g., vitreous opacity, glaucoma, dry eyes, ocular amyloid angiopathy, retinal detachment).

Techniques: Diagnostic Assay

Journal: Journal of Clinical Medicine

Article Title: Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis †

doi: 10.3390/jcm14196821

Figure Lengend Snippet: Median age of participants with TTR variants at genetic testing in ( a ) GeneAct ® and ( b ) TTR positivity by age range in Alnylam Act ® . 1 Includes 6 participants with variants of uncertain significance. 1H = first half of the year; 2H = second half of the year.

Article Snippet: Individuals eligible for testing in the Alnylam Act ® program were ≥18 years of age with ≥1 ATTRv high index of suspicion indicator that included family history of ATTRv amyloidosis; positive imaging consistent with amyloid (technetium, cardiac magnetic resonance, strain echo); or positive biopsy for TTR amyloid; or ≥2 ATTRv index of suspicion indicators that included sensory and/or motor neuropathy (e.g., neuropathic pain, altered sensation, numbness and tingling, muscle weakness, impaired balance, difficulty walking, carpal tunnel syndrome-associated neuropathy, electromyography/nerve conduction study abnormalities); autonomic dysfunction (e.g., nausea and vomiting, changes in gastrointestinal motility, orthostatic hypotension, sexual dysfunction, bladder dysfunction); heart disease (e.g., cardiomyopathy, restrictive physiology, hypertrophy, arrhythmias, conduction abnormalities, heart failure, abnormal cardiac imaging); musculoskeletal indicators (history of carpal tunnel syndrome, back pain/lumbar spinal stenosis, rotator cuff injury); renal abnormalities (e.g., renal insufficiency and/or proteinuria); and ocular changes (e.g., vitreous opacity, glaucoma, dry eyes, ocular amyloid angiopathy, retinal detachment).

Techniques:

Journal: Journal of Clinical Medicine

Article Title: Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis †

doi: 10.3390/jcm14196821

Figure Lengend Snippet: Presenting signs or symptoms in participants with TTR variants in ( a ) GeneAct ® ; and in ( b ) TTR -positive, TTR V122I (p.V142I) variant-positive, and TTR -negative participants in Alnylam Act ® . 1 Confirmed cases of ocular amyloidosis where a pathogenic or likely pathogenic TTR variant is present. 2 A101T was associated with Parkinson’s disease-like symptoms. 3 D74H (p.D94H) was associated with paraparesis. 4 Data available for 38 of 101 participants with variants in the TTR gene. Multiple symptoms may be reported by the same patient. MRI = magnetic resonance imaging.

Article Snippet: Individuals eligible for testing in the Alnylam Act ® program were ≥18 years of age with ≥1 ATTRv high index of suspicion indicator that included family history of ATTRv amyloidosis; positive imaging consistent with amyloid (technetium, cardiac magnetic resonance, strain echo); or positive biopsy for TTR amyloid; or ≥2 ATTRv index of suspicion indicators that included sensory and/or motor neuropathy (e.g., neuropathic pain, altered sensation, numbness and tingling, muscle weakness, impaired balance, difficulty walking, carpal tunnel syndrome-associated neuropathy, electromyography/nerve conduction study abnormalities); autonomic dysfunction (e.g., nausea and vomiting, changes in gastrointestinal motility, orthostatic hypotension, sexual dysfunction, bladder dysfunction); heart disease (e.g., cardiomyopathy, restrictive physiology, hypertrophy, arrhythmias, conduction abnormalities, heart failure, abnormal cardiac imaging); musculoskeletal indicators (history of carpal tunnel syndrome, back pain/lumbar spinal stenosis, rotator cuff injury); renal abnormalities (e.g., renal insufficiency and/or proteinuria); and ocular changes (e.g., vitreous opacity, glaucoma, dry eyes, ocular amyloid angiopathy, retinal detachment).

Techniques: Variant Assay, Magnetic Resonance Imaging

Journal: Journal of Clinical Medicine

Article Title: Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis †

doi: 10.3390/jcm14196821

Figure Lengend Snippet: ( a ) Number of test providers by specialty and ( b ) TTR positivity rate by specialty in Alnylam Act ® . 1 Other specialties included oncology, primary care, obstetrics, gynecology, pathology, surgery, and emergency medicine.

Article Snippet: Individuals eligible for testing in the Alnylam Act ® program were ≥18 years of age with ≥1 ATTRv high index of suspicion indicator that included family history of ATTRv amyloidosis; positive imaging consistent with amyloid (technetium, cardiac magnetic resonance, strain echo); or positive biopsy for TTR amyloid; or ≥2 ATTRv index of suspicion indicators that included sensory and/or motor neuropathy (e.g., neuropathic pain, altered sensation, numbness and tingling, muscle weakness, impaired balance, difficulty walking, carpal tunnel syndrome-associated neuropathy, electromyography/nerve conduction study abnormalities); autonomic dysfunction (e.g., nausea and vomiting, changes in gastrointestinal motility, orthostatic hypotension, sexual dysfunction, bladder dysfunction); heart disease (e.g., cardiomyopathy, restrictive physiology, hypertrophy, arrhythmias, conduction abnormalities, heart failure, abnormal cardiac imaging); musculoskeletal indicators (history of carpal tunnel syndrome, back pain/lumbar spinal stenosis, rotator cuff injury); renal abnormalities (e.g., renal insufficiency and/or proteinuria); and ocular changes (e.g., vitreous opacity, glaucoma, dry eyes, ocular amyloid angiopathy, retinal detachment).

Techniques:

Journal: Journal of Clinical Medicine

Article Title: Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis †

doi: 10.3390/jcm14196821

Figure Lengend Snippet: ( a ) Number of tests performed by test type and ( b ) TTR positivity by test type in Alnylam Act ® . 1 Combinations of the three test types.

Article Snippet: Individuals eligible for testing in the Alnylam Act ® program were ≥18 years of age with ≥1 ATTRv high index of suspicion indicator that included family history of ATTRv amyloidosis; positive imaging consistent with amyloid (technetium, cardiac magnetic resonance, strain echo); or positive biopsy for TTR amyloid; or ≥2 ATTRv index of suspicion indicators that included sensory and/or motor neuropathy (e.g., neuropathic pain, altered sensation, numbness and tingling, muscle weakness, impaired balance, difficulty walking, carpal tunnel syndrome-associated neuropathy, electromyography/nerve conduction study abnormalities); autonomic dysfunction (e.g., nausea and vomiting, changes in gastrointestinal motility, orthostatic hypotension, sexual dysfunction, bladder dysfunction); heart disease (e.g., cardiomyopathy, restrictive physiology, hypertrophy, arrhythmias, conduction abnormalities, heart failure, abnormal cardiac imaging); musculoskeletal indicators (history of carpal tunnel syndrome, back pain/lumbar spinal stenosis, rotator cuff injury); renal abnormalities (e.g., renal insufficiency and/or proteinuria); and ocular changes (e.g., vitreous opacity, glaucoma, dry eyes, ocular amyloid angiopathy, retinal detachment).

Techniques: