A novel compound heterozygote (FAP ATTR Arg104His/ ATTR Val30Met) with high serum transthyretin (TTR) and retinol binding protein (RBP) levels

A 64-year-old Japanese male suffering from very slowly progressive amyloido sis was studied by immunohistopathologic, mass spectrometric, and molecular genetic methods. After confirming the immunoreactivity of transthyretin (T TR) in the amyloid deposits using an anti-TTR polyclonal antibody, matrix-a ssisted laser desorption ionization/time-of-flight-mass spectrometry (MALDI /TOF-MS) was employed to look for the presence of variant TTR(s) in the ser um. Two variant forms of TTR, one with a molecular weight 32 Da greater and another with a molecular weight 19 Da less than that of normal TTR encoded by the two respective alleles, were detected in this patient. Direct seque nce analysis confirmed the presence of a double substitution: one at codon 30 from GTG (Val) to ATG; (Met) and the other at codon 104 from CGC (Arg) t o CAC (His) in the two alleles, MALDI/TOF-MS of the parents of the proband revealed that his father was a heterozygote of ATTR Arg104His and his mothe r was a heterozygote of ATTR Val30Met, The total TTR and retinol binding pr otein (RBP) concentrations in the serum samples of the proband were very hi gh compared with those of FAP ATTR Val30Met patients and control subjects. We report here a new compound heterozygote in the TTR gene with familial am yloidotic polyneuropathy (FAP). (C) 1999 Academic Press.