Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population: Penetrance of ATTR Val30Met mutation in Sweden

International audienceTransthyretin (TTR) familial amyloid polyneuropathies (FAP) are autosomal dominant devastating afflictions, first described in Portugal, later in Japan and Sweden, now recognized worldwide. The TTR-Val30Met mutation is the most common, and depending on the geographic origin, a wide variation in age at onset of the disease is observed. In Europe, northern Sweden is the second most important area of the disease, and a late age of onset of 56 years has been reported. The present work aims to estimate the penetrance in TTR-Val30Met Swedish families. Genealogical investigations, clinical data and genotyping were obtained in 77 TTR-Val30Met Swedish families. The penetrance in Val30Met carriers and variation within the endemic area, according to gender and transmitting parents was calculated by a newly developed bias free method. The penetrance estimates were low i.e.1.7% and 22% at age 30 and 60 years, respectively and far from complete (69%), by age 90 years. Differences between Piteå and Skellefteå regions were observed. Moreover, penetrance was significantly higher when the mutation was inherited from the mother than from the father. The low penetrance observed in TTR-FAP kindreds and its variations are important information for the genetic counselling and treatment of Swedish FAP- patients and their families