Phenotype Heterogeneity and Genotype Correlation of MAPT Mutations in a Chinese PUMCH Cohort.
Frontotemporal lobar degeneration
Microtubule-associated protein tau
Next generation sequencing
Phenotype
Variations
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
24
07
2020
accepted:
25
09
2020
pubmed:
3
10
2020
medline:
20
11
2021
entrez:
2
10
2020
Statut:
ppublish
Résumé
Frontotemporal dementia (FTD) is a heterogeneous disease both clinically and pathologically. Genetic mutation in microtubule-associated protein tau (MAPT) is the most common cause of FTD, and the phenotype is related to the mutation location. However, the phenotype and genotype correlation varies somewhat among different cohorts and ethnicities. Whole-genome next-generation sequencing (NGS) was carried out for 1351 patients with dementia at Peking Union Medical College Hospital. MAPT variations classified as pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected, and the phenotype-genotype correlation was analyzed with a concurrent literature review. Twenty-four patients were enrolled; 8 patients carrying the D177V mutation are discussed separately. The average onset age was young, and most of them had a positive family history. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Most structural MRIs showed asymmetrical atrophy of the temporal lobe, with/without similar changes in the frontal lobe. L266V carriers presented with youngest onset typical behavior variant FTD or aphasia; P301L carriers presented with behavior variant FTD or aphasia. Functional MRI and molecular imaging also showed that the involved areas were similar to those with structural atrophy. D296N carriers presented atypical parkinsonism and cognitive dysfunction at older ages. Eight D177V carriers had extraordinarily different manifestations. The clinical phenotype of most of them was not FTD, though cerebral vascular lesions were obvious in some of them. MAPT mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps. The D177V mutation is possibly not directly pathogenic in our cohort. Some of the variants might increase the genetic risk of neurodegenerative diseases.
Identifiants
pubmed: 33006106
doi: 10.1007/s12031-020-01723-4
pii: 10.1007/s12031-020-01723-4
doi:
Substances chimiques
MAPT protein, human
0
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1015-1022Subventions
Organisme : CAMS Innovation fund for medical sciences
ID : 2016-I2M-1-004
Organisme : National Natural Science Foundation of China
ID : 81550021
Organisme : National Natural Science Foundation of China
ID : 30470618
Organisme : 13th five years' national key research and development program of China
ID : 2016YFC1306300
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