title: 'PrP systemic deposition disease': clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178.
abstract: OBJECTIVE
  A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously.
  
  
  METHODS
  Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control).
  
  
  RESULTS
  Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon.
  
  
  CONCLUSIONS
  The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology.
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuzono
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Honda
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Morihara
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Deguchi
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hishikawa
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kono
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwaki
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D000328:Adult; D003062:Codon; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D017096:Prion Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions
keywords: autonomic failure; hereditary neuropathy; neuropathology; peripheral neuropathy; prion disease