Genetic anticipation in Portuguese kindreds with familial amyloidotic polyneuropathy is unlikely to be caused by triplet repeat expansions

Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant ty pe of amyloidosis resulting from the deposition of transthyretin (ATTR) var iants in the peripheral and autonomic nervous systems. ATTR V30M-associated FAP exhibits marked genetic anticipation in some families, with clinical s ymptoms developing at an earlier age in successive generations. The genetic basis of this phenomenon in FAP is unknown. Anticipation has been associat ed with the dynamic expansion of trinucleotide repents in several neurodege nerative disorders, such as Huntington disease, myotonic dystrophy, and fra gile X syndrome. We have used the repeat expansion detection (RED) assay to screen affected members of Portuguese FAP kindreds for expansion of any of the ten possible trinucleotide repeats. Nine generational pairs with diffe rences in their age of onset greater than 12 years and a control pair with identical ages of onset were tested. No major differences were found in the lengths of the ten trinucleotide repeats analyzed, The distribution of the maximal repeat sizes was consistent with reported studies in unrelated ind ividuals with no known genetic disease, The present data do not support a r ole for trinucleotide repeat expansions as the molecular mechanism underlyi ng anticipation in Portuguese FAP.