PMID- 15615814
OWN - NLM
STAT- MEDLINE
DCOM- 20050420
LR  - 20071114
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Linking)
VI  - 128
IP  - Pt 4
DP  - 2005 Apr
TI  - Longitudinal characterization of two siblings with frontotemporal dementia and 
      parkinsonism linked to chromosome 17 associated with the S305N tau mutation.
PG  - 752-72
AB  - The background to this study began with the reporting of two Japanese kindreds 
      with the S305N tau mutation. Although the pathological findings in the autopsied 
      cases were well characterized, only limited ante-mortem data were presented. In 
      this study, longitudinal characterization was carried out in two siblings of 
      European ancestry found to have frontotemporal dementia and parkinsonism linked 
      to chromosome 17 (FTDP-17) through comprehensive neurobehavioural examinations 
      and other scales at approximate 6-month intervals. Scales included the 
      Mini-Mental State Examination, Short Test of Mental Status, modified motor 
      subtest of the Unified Parkinson's Disease Rating Scale, detailed 
      neuropsychological testing, and the Neuropsychiatric Inventory. Changes in 
      whole-brain volume and ventricular volume were measured from serial MRI studies. 
      All members of the kindred underwent molecular genetic analyses to elucidate the 
      mechanism of inheritance. The missense mutation in tau, S305N, was detected in 
      the proband (onset age 30), who has undergone serial evaluations for almost 4 
      years. Her older sister (onset age 36) was subsequently found to have the same 
      mutation, and has undergone serial evaluations for 2 years. This mutation is 
      absent in both parents and the only other sibling, and non-paternity was excluded 
      by additional analyses. The siblings have exhibited cognitive and behavioural 
      features typical of FTDP-17, which have proved challenging to manage despite 
      aggressive pharmacological and behavioural therapies. The proband's sister has 
      demonstrated an atypical profile of impairment on neuropsychological testing. 
      Both siblings have developed striking atrophy of the anterior part of temporal 
      lobes and moderate atrophy of the dorsolateral and orbitofrontal cortical 
      regions, which in both cases is relatively symmetrical. The annualized changes in 
      whole-brain volume and ventricular volume, respectively, were -35.2 ml/year 
      (3.23% decrease per year) and +20.75 ml/year (16.93% increase per year) for the 
      proband, and -30.75 ml/year (2.77% decrease per year) and +5.01 ml/year (3.11% 
      increase per year) for the proband's sister. In conclusion, the mutation in these 
      siblings may have arisen during oogenesis in the mother and probably represents 
      germline mosaicism. Although both patients have exhibited the typical cognitive 
      and behavioural features of FTDP-17, one patient is exhibiting an atypical 
      neuropsychological profile. Also, despite a similar topographic pattern of 
      progressive atrophy on MRI, the rates of change in whole-brain volume and 
      ventricular volume between the two patients are quite different. These findings 
      have implications for future drug trial development in FTDP-17 and the sporadic 
      tauopathies.
FAU - Boeve, Bradley F
AU  - Boeve BF
AD  - Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, 
      MN 55905, USA. bboeve@mayo.edu
FAU - Tremont-Lukats, Ivo W
AU  - Tremont-Lukats IW
FAU - Waclawik, Andrew J
AU  - Waclawik AJ
FAU - Murrell, Jill R
AU  - Murrell JR
FAU - Hermann, Bruce
AU  - Hermann B
FAU - Jack, Clifford R Jr
AU  - Jack CR Jr
FAU - Shiung, Maria M
AU  - Shiung MM
FAU - Smith, Glenn E
AU  - Smith GE
FAU - Nair, Anil R
AU  - Nair AR
FAU - Lindor, Noralane
AU  - Lindor N
FAU - Koppikar, Vinaya
AU  - Koppikar V
FAU - Ghetti, Bernardino
AU  - Ghetti B
LA  - eng
GR  - P30 AG10133/AG/NIA NIH HHS/United States
GR  - P50 AG 16574/AG/NIA NIH HHS/United States
GR  - R01 NS 37431/NS/NINDS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041222
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (tau Proteins)
SB  - IM
MH  - Adult
MH  - Brain/pathology
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Dementia/complications/*genetics/pathology
MH  - Female
MH  - Humans
MH  - Longitudinal Studies
MH  - Magnetic Resonance Imaging
MH  - Mental Disorders/etiology
MH  - *Mutation
MH  - Neuropsychological Tests
MH  - Parkinsonian Disorders/complications/*genetics/pathology
MH  - Pedigree
MH  - Siblings
MH  - tau Proteins/*genetics
EDAT- 2004/12/24 09:00
MHDA- 2005/04/21 09:00
CRDT- 2004/12/24 09:00
PHST- 2004/12/24 09:00 [pubmed]
PHST- 2005/04/21 09:00 [medline]
PHST- 2004/12/24 09:00 [entrez]
AID - awh356 [pii]
AID - 10.1093/brain/awh356 [doi]
PST - ppublish
SO  - Brain. 2005 Apr;128(Pt 4):752-72. doi: 10.1093/brain/awh356. Epub 2004 Dec 22.