ClinVar

In a kindred with systemic amyloidosis (AMYLD1; 105210) presenting as peripheral neuropathy in the sixth and seventh decades of life, Uemichi et al. (1992) demonstrated a T-to-C transition at nucleotide 1038 of the TTR gene leading to substitution of arginine for cysteine at position 10 of the TTR protein molecule (C10R). The mutation created a new restriction recognition site, thus allowing easy diagnosis. The mutation was identified in 7 persons: none of 3 female mutant gene carriers, who were 87, 85, and 76 years old, had symptoms of the disease, while 4 of 5 male carriers, including 1 patient whose DNA was not available for testing, developed the disease in their fifties or sixties. It had been observed in other types of FAP that males are affected predominantly or at earlier ages than females. Affected subjects showed sensory and motor neuropathy, bowel disorder, sexual impotence, cardiomyopathy, and vitreous opacity, but no kidney dysfunction. Benson (2001) noted that arg10 replaces the only cysteine in the transthyretin molecule.