Stroke
Gene: TTR
Being a syndrome, individuals with TTR- related amyloidosis can present with multi-systemic phenotypes including, polyneuropathy, carpal tunnel syndrome, cardiomyopathy, gastrointestinal features, autonomic insufficiency, and renal insufficiency.
The mechanism for disease is gain of function, as mutation causes either tetramer dissociation or monomer denaturation, which both contribute to the formation of amyloid fibrils in tissue (Sekijima, 2015; PMID 25604431). All reported variants in affected individuals are missense.
Some individuals with Hereditary ATTR amyloidosis present with features of hypertrophic cardiomyopathy (HCM) and/or restrictive cardiomyopathy (RCM)... Several variants including TTR-V30M, TTR-T60A, and TTR-V122L are the most commonly associated with cardiac amyloidosis (Siddiqi and Ruberg, 2017 PMID 28739313).
For the neuropathy sub-phenotype, the current literature provides additional evidence including further neuropathy cases associated to various TTR mutations such as p.Val50Met (PMIDs: 8071954, 19180884, 24101130) and p.Leu75Pro (1351039, 7910950, 31319424)Created: 30 Mar 2022, 10:55 p.m. | Last Modified: 30 Mar 2022, 10:55 p.m.
Panel Version: 0.12323
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Amyloidosis, hereditary, transthyretin-related, MIM #105210; Carpal tunnel syndrome, familial, MIM# 115430
Publications
Mode of pathogenicity
Other
PMID: 12771253: 14 individuals from one family with oculoleptomeningeal amyloidosis, stroke like episodes, found p.Tyr69His - variable expression.
PMID: 32789836; 10 unrelated male patients all with cardiac amyloidosis, 7 patients had p.Phe53Leu, 2 had p.Glu109Lys and 1 had p.Ala101Val. One died from stroke.
PMID: 15377697: two Japanese brothers with familial leptomeningeal amyloidosis; p.Asp18Gly; same variant previously reported in one other case.
PMID: 18579156: Thr49Pro in a 53 year-old man presented with recurrent episodes of transient aphasia and right hand stiffness, headaches, and peripheral neuropathy.
Variants appear to be associated with leptomeningeal amyloidosis leading to vessel fragility and SAH riskCreated: 10 Mar 2021, 1:27 a.m. | Last Modified: 10 Mar 2021, 1:27 a.m.
Panel Version: 0.70
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Gene: ttr has been classified as Green List (High Evidence).
Phenotypes for gene: TTR were changed from Amyloidogenic transthyretin amyloidosis to Amyloidosis, hereditary, transthyretin-related, MIM# 105210
Publications for gene: TTR were set to
gene: TTR was added gene: TTR was added to Stroke. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: TTR were set to Amyloidogenic transthyretin amyloidosis