Phenotypic variability of TTR Val122Ile mutation: a Caucasian patient with axonal neuropathy and normal heart

Val122Ile is one of more than 100 mutations in transthyretin gene (TTR) that is associated with familial amyloidotic polyneuropathy (FAP), with a prevalence as high as 3.9% in Afro-Americans. It has, as main clinical expression, a hypertrophic restrictive cardiomyopathy with mild or no neurological symptoms. We report the first Caucasian patient carrying Val122Ile mutation with an axonal neuropathy and no cardiac involvement. Our case report without cardiac involvement suggests the possible underestimation of Val122Ile mutation in non-African population. In addition, with the recent discovery of gene modifiers and the ‘‘cisregulatory’’ hypothesis in Val30Met, we have now greater needs for TTR genetic analysis than in the past as well as more uncertainties in family genetic counseling.