Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population

• Main Authors: Hellman, Urban, Alarcon, Flora, Lundgren, Hans Eric, Suhr, Ole, Bonaïti-Pellié, Catherine, Planté-Bordeneuve, Violaine
• Other Authors: Medical and Clinical Genetics, Umeå University, Sweden, Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, Service de neurologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Stéroïdes et système nerveux : physiopathologie moléculaire et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2008
• Subjects: tranthyretin; amyloidosis; genetics; penetrance; Swedish families; [SDV.GEN]Life Sciences [q-bio]/Genetics; Northern Sweden; Piteå
• Online Access: https://inserm.hal.science/inserm-00359758; https://inserm.hal.science/inserm-00359758/document; https://inserm.hal.science/inserm-00359758/file/NAH_Suede_def.pdf

International audience Transthyretin (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.