title: A genealogical and clinical study of the phenotypical variation within the Swedish transthyretin His88Arg (p. His108Arg) amyloidosis family.
abstract: In 2005 we reported the first case of transthyretin His88Arg (p. His108Arg) amyloidosis, a mutation characterised by cardiomyopathy. Six additional gene carriers of whom five have clinical symptoms of disease have now been identified in Sweden, and we have been able to identify a possible founder and to characterise the Swedish phenotype of the transthyretin (TTR) His88Arg mutation. Genealogical studies of church records were used to identify the individuals with the disease and their families. Routine clinical investigations of neurological and heart manifestation of the disease were utilised. We found that genealogically all seven individuals were related and originated from the same region in Sweden. Amyloid deposits were demonstrated in biopsies and the TTR His88Arg mutation was identified in all patients. Patients had a late onset disease (≥ 50 years of age) and all exhibited a severe amyloid cardiomyopathy. A pronounced peripheral axonal neuropathy was with certainty demonstrated in one patient only, who also was operated for a magnetic resonance confirmed spinal stenosis, however, without any effect on his neurological symptoms. Five of the patients had carpal tunnel syndrome. The first reported case is now deceased from cardiac failure. One patient has had a sequential heart and liver transplantation. One gene carrier had no symptoms or findings of disease on latest evaluation at the age of 44.
  
  
  CONCLUSIONS
  the Swedish TTRHis88Arg patients all have a common Swedish founder. Cardiomyopathy with heart failure, as well as carpal tunnel syndrome and spinal stenosis were early signs of disease; but peripheral neuropathy was present in one patient before symptoms of cardiomyopathy so the phenotypical presentation of this mutation is variable.
authors.affiliation: Cardiology, Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Urban
authors.initials: U
authors.lastname: Hellman
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Hans-Erik
authors.initials: HE
authors.lastname: Lundgren
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.affiliation: Department of Medicine, Enköpings Lasarett, Enköping, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Stafberg
authors.affiliation: Department of Haematology, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
authors.affiliation: Department of Medicine, Mora Lasarett, Mora, Sweden.
authors.forename: Sascha
authors.initials: S
authors.lastname: Tachlinski
authors.affiliation: Department of Cardiology, Falu Lasarett, Falun, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Guggi
authors.affiliation: Department of Medicine, Falu Lasarett, Falun, Sweden.
authors.forename: Max
authors.initials: M
authors.lastname: Flogegård
authors.affiliation: Department of Cardiology, Mälarsjukhuset, Eskildtuna, Sweden.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Hamid
authors.affiliation: Department of Clinical Science, Genetic & Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Escher
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. Electronic address: ole.suhr@umu.se.
authors.forename: Ole B
authors.initials: OB
authors.lastname: Suhr
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000473:pathology*; D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics*; D002349:Carpal Tunnel Syndrome / Q000150:complications / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006801:Humans; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics*; D011228:Prealbumin / Q000235:genetics*; D013130:Spinal Stenosis / Q000150:complications / Q000235:genetics; D013548:Sweden; D044465:White People / Q000235:genetics
chemical_list: D011228:Prealbumin
keywords: Amyloidosis-hereditary; Cardiomyopathy; Genealogy; Neuropathy; Transthyretin