Abstract
Objective Patients with corticobasal syndrome (CBS) present with heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a genetic analysis of microtubule-associated protein tau (MAPT). Methods We performed a genetic evaluation of MAPT mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip genotyping array. Results We identified 2 patients with CBS heterozygous for a rare mutation in MAPT (p.V363I) that is located in the highly conserved microtubule-binding domain. One patient was pathologically confirmed and demonstrated extensive 4-repeat-tau-positive thread pathology, achromatic neurons, and astrocytic plaques consistent with corticobasal degeneration (CBD). Conclusions We report 2 CBS cases carrying the rare p.V363I MAPT mutation, one of which was pathologically confirmed as CBD. Our findings support the notion that this rare coding change is pathogenic.
| Original language | English (US) |
|---|---|
| Article number | 347 |
| Journal | Neurology: Genetics |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 1 2019 |
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ASJC Scopus subject areas
- Clinical Neurology
- Genetics(clinical)
Cite this
MAPT p.V363I mutation A rare cause of corticobasal degeneration. / Ahmed, Sarah; Fairen, Monica Diez; Sabir, Marya S.; Pastor, Pau; Ding, Jinhui; Ispierto, Lourdes; Butala, Ankur; Morris, Christopher M.; Schulte, Claudia; Gasser, Thomas; Jabbari, Edwin; Pletnikova, Olga; Morris, Huw R.; Troncoso, Juan; Gelpi, Ellen; Pantelyat, Alexander; Scholz, Sonja W.
In: Neurology: Genetics, Vol. 5, No. 4, 347, 01.08.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MAPT p.V363I mutation A rare cause of corticobasal degeneration
AU - Ahmed, Sarah
AU - Fairen, Monica Diez
AU - Sabir, Marya S.
AU - Pastor, Pau
AU - Ding, Jinhui
AU - Ispierto, Lourdes
AU - Butala, Ankur
AU - Morris, Christopher M.
AU - Schulte, Claudia
AU - Gasser, Thomas
AU - Jabbari, Edwin
AU - Pletnikova, Olga
AU - Morris, Huw R.
AU - Troncoso, Juan
AU - Gelpi, Ellen
AU - Pantelyat, Alexander
AU - Scholz, Sonja W.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Objective Patients with corticobasal syndrome (CBS) present with heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a genetic analysis of microtubule-associated protein tau (MAPT). Methods We performed a genetic evaluation of MAPT mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip genotyping array. Results We identified 2 patients with CBS heterozygous for a rare mutation in MAPT (p.V363I) that is located in the highly conserved microtubule-binding domain. One patient was pathologically confirmed and demonstrated extensive 4-repeat-tau-positive thread pathology, achromatic neurons, and astrocytic plaques consistent with corticobasal degeneration (CBD). Conclusions We report 2 CBS cases carrying the rare p.V363I MAPT mutation, one of which was pathologically confirmed as CBD. Our findings support the notion that this rare coding change is pathogenic.
AB - Objective Patients with corticobasal syndrome (CBS) present with heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a genetic analysis of microtubule-associated protein tau (MAPT). Methods We performed a genetic evaluation of MAPT mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip genotyping array. Results We identified 2 patients with CBS heterozygous for a rare mutation in MAPT (p.V363I) that is located in the highly conserved microtubule-binding domain. One patient was pathologically confirmed and demonstrated extensive 4-repeat-tau-positive thread pathology, achromatic neurons, and astrocytic plaques consistent with corticobasal degeneration (CBD). Conclusions We report 2 CBS cases carrying the rare p.V363I MAPT mutation, one of which was pathologically confirmed as CBD. Our findings support the notion that this rare coding change is pathogenic.
UR - http://www.scopus.com/inward/record.url?scp=85073784970&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073784970&partnerID=8YFLogxK
U2 - 10.1212/NXG.0000000000000347
DO - 10.1212/NXG.0000000000000347
M3 - Article
C2 - 31404212
AN - SCOPUS:85073784970
VL - 5
JO - Neurology: Genetics
JF - Neurology: Genetics
SN - 2376-7839
IS - 4
M1 - 347
ER -