Amyloidosis
Gene: TTR
The kidney is one of the main organs affected by transthyretin amyloidosis.
Sources: LiteratureCreated: 10 Sep 2024, 7:11 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hereditary ATTR amyloidosis MONDO:0017132
Publications
Variants in this GENE are reported as part of current diagnostic practice
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
Gene: ttr has been classified as Green List (High Evidence).
Gene: ttr has been classified as Green List (High Evidence).
gene: TTR was added gene: TTR was added to Renal Amyloidosis. Sources: Literature Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TTR were set to 20301373; 38484868 Phenotypes for gene: TTR were set to hereditary ATTR amyloidosis MONDO:0017132 Review for gene: TTR was set to GREEN gene: TTR was marked as current diagnostic