Clinical characterization of a kindred with a novel 12-octapeptide repeat insertion in the prion protein gene

Neeraj Kumar, Bradley F Boeve, Brendon P. Boot, Carolyn F. Orr, Joseph Duffy, Bryan K Woodruff, Anil K. Nair, Jay Ellison, Karen Kuntz, Kejal M Kantarci, Clifford R Jr. Jack, Barbara F. Westmoreland, Julie A Fields, Matthew Baker, Rosa V Rademakers, Joseph E Parisi, Dennis W Dickson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective: To report the clinical, electroencephalographic, and neuroradiologic findings in a kindred with a novel insertion in the prion protein gene, PRNP. Design: Clinical description of a kindred. Setting: Mayo Clinic Alzheimer Disease Research Center (Rochester, Minnesota). Subjects: Two pathologically confirmed cases and their relatives. Main Outcome Measures: Clinical features, electroencephalographic patterns, magnetic resonance imaging abnormalities, genetic analyses, and neuropathologic features. Results: The proband was a woman with clinical and neuroimaging features of atypical frontotemporal dementia and ataxia. Generalized tonic-clonic seizures developed later in the disease course, and electroencephalography revealed spike and wave discharges but no periodic sharpwave complexes. Her affected sister and father also exhibited frontotemporal dementia-like features, and both experienced generalized tonic-clonic seizures and gait ataxia late in the disease course. Genetic analyses in the proband identified a novel defect in PRNP, with 1 mutated allele carrying a 288-base pair insertion consisting of 12 octapeptide repeats. Neuropathologic examination of the proband and her sister revealed prion protein-positive plaques and widespread tau-positive tangles. Conclusions: This kindred has a unique combination of clinical and neuropathologic features associated with the largest base pair insertion identified to date in PRNP and underscores the need to consider familial prion disease in the differential diagnosis of a familial frontotemporal dementia-like syndrome.

Original languageEnglish (US)
Pages (from-to)1165-1170
Number of pages6
JournalArchives of Neurology
Volume68
Issue number9
DOIs
StatePublished - Sep 2011

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Frontotemporal Dementia
Base Pairing
Siblings
Seizures
Gait Ataxia
Genes
Prion Diseases
Ataxia
Neuroimaging
Fathers
Dementia
Electroencephalography
Alzheimer Disease
Differential Diagnosis
Alleles
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
Research
Prion Proteins
Insertion

ASJC Scopus subject areas

  • Clinical Neurology

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Clinical characterization of a kindred with a novel 12-octapeptide repeat insertion in the prion protein gene. / Kumar, Neeraj; Boeve, Bradley F; Boot, Brendon P.; Orr, Carolyn F.; Duffy, Joseph; Woodruff, Bryan K; Nair, Anil K.; Ellison, Jay; Kuntz, Karen; Kantarci, Kejal M; Jack, Clifford R Jr.; Westmoreland, Barbara F.; Fields, Julie A; Baker, Matthew; Rademakers, Rosa V; Parisi, Joseph E; Dickson, Dennis W.

In: Archives of Neurology, Vol. 68, No. 9, 09.2011, p. 1165-1170.

Research output: Contribution to journalArticle

Kumar, Neeraj ; Boeve, Bradley F ; Boot, Brendon P. ; Orr, Carolyn F. ; Duffy, Joseph ; Woodruff, Bryan K ; Nair, Anil K. ; Ellison, Jay ; Kuntz, Karen ; Kantarci, Kejal M ; Jack, Clifford R Jr. ; Westmoreland, Barbara F. ; Fields, Julie A ; Baker, Matthew ; Rademakers, Rosa V ; Parisi, Joseph E ; Dickson, Dennis W. / Clinical characterization of a kindred with a novel 12-octapeptide repeat insertion in the prion protein gene. In: Archives of Neurology. 2011 ; Vol. 68, No. 9. pp. 1165-1170.
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AU - Orr, Carolyn F.

AU - Duffy, Joseph

AU - Woodruff, Bryan K

AU - Nair, Anil K.

AU - Ellison, Jay

AU - Kuntz, Karen

AU - Kantarci, Kejal M

AU - Jack, Clifford R Jr.

AU - Westmoreland, Barbara F.

AU - Fields, Julie A

AU - Baker, Matthew

AU - Rademakers, Rosa V

AU - Parisi, Joseph E

AU - Dickson, Dennis W

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