title: Report of five rare or previously unknown amyloidogenic transthyretin mutations disclosed in Sweden.
abstract: The number of amyloidogenic transthyretin (TTR) mutations described in the literature is more than 100. However, for several mutations, the phenotype has been described in a few individuals only; thus, the knowledge of the clinical course and the outcome after therapeutical interventions such as liver transplantation is limited. We describe the phenotype associated with five rare amyloidogenic TTR mutations that lately were discovered in Sweden: ATTR Val30Leu, Ala45Ser, Leu55Gln, Gly57Arg and Tyr69His of which ATTR Gly57Arg is previously unknown. The symptoms at onset differed, but cardiomyopathy and peripheral neuropathy were observed in all except the ATTR Tyr69His mutation. Likewise, carpal tunnel syndrome was found or had been present in all cases except the case with the ATTR Val30Leu mutation. The phenotype of the ATTR Tyr69His mutation was characterised by oculo-meningeal symptoms with seizures and a steadily progressing dementia, symptoms rarely found in ATTR amyloidosis, but similar to those previously described for this mutation, where all cases appear to originate from one Swedish family. Two patients with the ATTR Leu55Gln and Ala45Ser mutations have been subjected to liver transplantation, but echocardiographic examination has revealed an increasing cardiomyopathy after transplantation in both cases, the ATTR Leu55Gln patient succumbed 2 years after transplantation from progressive disease.
authors.affiliation: Department of Medicine, Umeå University Hospital, Umeå, Sweden. ole.suhr@medicin.umu.se
authors.forename: Ole B
authors.initials: OB
authors.lastname: Suhr
authors.forename: Oluf
authors.initials: O
authors.lastname: Andersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Aronsson
authors.forename: Jenni
authors.initials: J
authors.lastname: Jonasson
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.forename: Christer
authors.initials: C
authors.lastname: Lundahl
authors.forename: Hans-Eric
authors.initials: HE
authors.lastname: Lundgren
authors.forename: Atle
authors.initials: A
authors.lastname: Melberg
authors.forename: Johan
authors.initials: J
authors.lastname: Nyberg
authors.forename: Malin
authors.initials: M
authors.lastname: Olsson
authors.forename: Arne
authors.initials: A
authors.lastname: Sandberg
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000209:etiology / Q000235:genetics*; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008875:Middle Aged; D009154:Mutation; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics*; D013548:Sweden; D044465:White People; D055815:Young Adult
chemical_list: D011228:Prealbumin