Abstract
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is caused by a mutation in the transthyretin (TTR) gene. Although classically described as rapidly progressive and life-threatening, recent studies on TTR-FAP show significant genetic and phenotypic heterogeneity depending on geographic localization. In light of new therapeutic advances and their implication for patient management, the aim of our study was to determine the prevalence of TTR-FAP within patients with idiopathic neuropathy in a North American population. We sequenced the TTR gene in a cohort of patients with idiopathic neuropathy. Genetic screening was performed in 110 patients from two neuromuscular clinics in Montreal, Canada. No variants of unknown significance or pathogenic mutations were detected in the TTR gene. Our study confirms that TTR-FAP is a rare entity in our patient population, and that diagnostic yield of screening all patients with idiopathic neuropathy is very low.
Highlights
Transthyretin (TTR) is a 127-amino-acid polypeptide mainly synthesized in the liver, which assembles to form a tetrameric protein that circulates in the bloodstream to transport thyroxin (T4) and retinol
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disease caused by mutations in the TTR gene
There were very few patients with associated cardiac or renal disease of unclear etiology. This is the first study looking at the prevalence of TTR-FAP within a North American population with idiopathic neuropathy
Summary
Transthyretin (TTR) is a 127-amino-acid polypeptide mainly synthesized in the liver, which assembles to form a tetrameric protein that circulates in the bloodstream to transport thyroxin (T4) and retinol. Mutations in the TTR gene destabilize the TTR tetramers and favor their dissociation into monomers that self-aggregate to form non-fibrillar soluble oligomers and protofibrils. These in turn assemble into insoluble amyloid fibrils which deposit in multiple organs, predominantly the heart and peripheral nerves.[1]. 119 point mutations in the TTR gene have been identified, the most common being Val30Met in Portuguese, Swedish, and Japanese populations.[2] Typically, patients present in their mid-20–40s with a rapidly progressing sensorimotor, length-dependent polyneuropathy, which predominantly affects unmyelinated and small myelinated fibers. Conclusion: Our study confirms that TTR-FAP is a rare entity in our patient population, and that diagnostic yield of screening all patients with idiopathic neuropathy is very low
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