title: Frequencies and geographic distributions of genetic mutations in transthyretin- and non-transthyretin-related familial amyloidosis.
abstract: Inherited forms of amyloidosis are rare; of these, transthyretin-related (ATTR) is the most common, but non-ATTR has been described as well. We studied a large case series of ATTR and a small series of non-ATTR to better determine the mutation frequencies and geographic distributions of these inherited forms of amyloidosis in the United States. We performed a retrospective cross-sectional study of 284 ATTR and non-ATTR patients seen at Mayo Clinic in Rochester, Minnesota, from 1 January 1970 through 29 January 2013. Mutations were identified by DNA sequencing, restriction fragment length polymorphism, or mass spectroscopy. The genetic testing method was unknown for several patients, but a small proportion were identified by family history or by classical clinical presentation associated with a specific mutation. The most common ATTR mutations were Thr60Ala (24%), Val30Met (15%), Val122Ile (10%), and Ser77Tyr (5%). Non-ATTR mutations included gelsolin (n = 3), apolipoprotein A-I (n = 6), apolipoprotein A-II (n = 1), fibrinogen A-α (n = 9), and lysozyme (n = 1). Although rare, ATTR and, to a lesser extent, non-ATTR are prevalent in the United States and should be considered for patients presenting in the appropriate clinical context.
authors.affiliation: Department of Internal Medicine.
authors.forename: D B
authors.initials: DB
authors.lastname: Zhen
authors.affiliation: Department of Internal Medicine.
authors.forename: P L
authors.initials: PL
authors.lastname: Swiecicki
authors.affiliation: Division of Hematology.
authors.forename: S R
authors.initials: SR
authors.lastname: Zeldenrust
authors.affiliation: Division of Hematology.
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Mauermann
authors.affiliation: Division of Hematology.
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D005843:Geography; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011228:Prealbumin / Q000235:genetics*; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: D011228:Prealbumin
keywords: amyloidosis; apolipoprotein; fibrinogen; gelsolin; hereditary; lysozyme; mutation; transthyretin