PMID- 34274155
OWN - NLM
STAT- MEDLINE
DCOM- 20211231
LR  - 20211231
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 106
DP  - 2021 Oct
TI  - A clinical, molecular genetics and pathological study of a FTDP-17 family with a 
      heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT 
      gene.
PG  - 343.e1-343.e8
LID - S0197-4580(21)00171-8 [pii]
LID - 10.1016/j.neurobiolaging.2021.05.010 [doi]
AB  - We report the first clinical-radiological-genetic-molecular-pathological study of 
      a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with 
      frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We 
      describe the clinical spectrum within this family and emphasize the association 
      between MAPT gene variants and motor neuron disease. This report of a second 
      family with FTDP-17 associated with c.823-10G>T MAPT variant strongly supports 
      pathogenicity of the variant and confirms it is a 4-repeat (4R) tauopathy. This 
      intronic point mutation, probably strengthens the polypyrimidine tract and alters 
      the splicing of exon 10 (10 nucleotides into intron 9) close to the 3' splice 
      site.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Olszewska, Diana A
AU  - Olszewska DA
AD  - Department of Neurology, Dublin Neurological Institute, Mater Misericordiae 
      University Hospital, Dublin, Ireland.
FAU - Fearon, Conor
AU  - Fearon C
AD  - Department of Neurology, Dublin Neurological Institute, Mater Misericordiae 
      University Hospital, Dublin, Ireland.
FAU - McGuigan, Christopher
AU  - McGuigan C
AD  - Department of Neurology, St Vincent's University Hospital, Dublin, Ireland.
FAU - McVeigh, Terri P
AU  - McVeigh TP
AD  - Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
FAU - Houlden, Henry
AU  - Houlden H
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London, UK.
FAU - Polke, James M
AU  - Polke JM
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London, UK.
FAU - Lawlor, Brian
AU  - Lawlor B
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London, UK.
FAU - Coen, Robert
AU  - Coen R
AD  - Mercer's Institute of Aging, St James's Hospital Dublin, Ireland.
FAU - Hutchinson, Michael
AU  - Hutchinson M
AD  - Mercer's Institute of Aging, St James's Hospital Dublin, Ireland.
FAU - Hutton, Michael
AU  - Hutton M
AD  - Department of Neurology, St Vincent's University Hospital, Dublin, Ireland.
FAU - Beausang, Alan
AU  - Beausang A
AD  - Eli Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, USA.
FAU - Delon, Isabelle
AU  - Delon I
AD  - Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
FAU - Brett, Francesca
AU  - Brett F
AD  - East Genomic Laboratory Hub, Cambridge University Hospital NHS Foundation Trust, 
      Addenbrooke's Treatment Centre, Hills Road, Cambridge, UK.
FAU - Sevastou, Ioanna
AU  - Sevastou I
AD  - Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
FAU - Seto-Salvia, Nuria
AU  - Seto-Salvia N
AD  - East Genomic Laboratory Hub, Cambridge University Hospital NHS Foundation Trust, 
      Addenbrooke's Treatment Centre, Hills Road, Cambridge, UK.
FAU - de Silva, Rohan
AU  - de Silva R
AD  - Department of Clinical and Movement Neuroscience, Reta Lila Weston Institute, UCL 
      Queen Square Institute of Neurology, London, UK.
FAU - Lynch, Tim
AU  - Lynch T
AD  - Department of Neurology, Dublin Neurological Institute, Mater Misericordiae 
      University Hospital, Dublin, Ireland; Health affairs, University College Dublin, 
      Dublin, Ireland; Ireland East Hospital Group, Dublin, Ireland. Electronic 
      address: tlynch@dni.ie.
LA  - eng
GR  - R01 NS076837/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210523
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (MAPT protein, human)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Aged
MH  - Brain/diagnostic imaging
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Exons/*genetics
MH  - Female
MH  - Frontotemporal Dementia/diagnostic imaging/*genetics/pathology
MH  - Genetic Association Studies/*methods
MH  - *Heterozygote
MH  - Humans
MH  - Introns/*genetics
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Motor Neuron Disease/genetics
MH  - Neuroimaging
MH  - Parkinsonian Disorders/diagnostic imaging/*genetics/pathology
MH  - Point Mutation/*genetics
MH  - Tauopathies/genetics
MH  - tau Proteins/*genetics
OTO - NOTNLM
OT  - Frontotemporal dementia
OT  - Genetics
OT  - Intron 9/exon 10 mutation
OT  - Neuropathology
OT  - c.823-10G>T
EDAT- 2021/07/19 06:00
MHDA- 2022/01/01 06:00
CRDT- 2021/07/18 20:28
PHST- 2020/12/23 00:00 [received]
PHST- 2021/04/17 00:00 [revised]
PHST- 2021/05/13 00:00 [accepted]
PHST- 2021/07/19 06:00 [pubmed]
PHST- 2022/01/01 06:00 [medline]
PHST- 2021/07/18 20:28 [entrez]
AID - S0197-4580(21)00171-8 [pii]
AID - 10.1016/j.neurobiolaging.2021.05.010 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2021 Oct;106:343.e1-343.e8. doi: 
      10.1016/j.neurobiolaging.2021.05.010. Epub 2021 May 23.