The heritability and genetics of frontotemporal lobar degeneration.
Neurology
; 73(18): 1451-6, 2009 Nov 03.
Article
en En
| MEDLINE
| ID: mdl-19884572
ABSTRACT
BACKGROUND:
Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder.METHODS:
We collected blood samples from a cohort of 225 patients with a diagnosis within the FTLD spectrum and examined the heritability of FTLD by giving each patient a family history score, from 1 (a clear autosomal dominant history of FTLD) through to 4 (no family history of dementia). We also looked for mutations in each of the 5 disease-causing genes (MAPT, GRN, VCP, CHMP2B, and TARDP) and the FUS gene, known to cause motor neuron disease.RESULTS:
A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had a clear autosomal dominant history (score of 1). Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable. Mutations were found in MAPT (8.9% of the cohort) and GRN (8.4%) but not in any of the other genes. Of the remaining patients without mutations but with a strong family history, 7 had pathologic confirmation, falling into 2 groups type 3 FTLD-TDP without GRN mutations (6) and FTLD-UPS (1).CONCLUSION:
These findings show that frontotemporal lobar degeneration (FTLD) is a highly heritable disorder but heritability varies between the different syndromes. Furthermore, while MAPT and GRN mutations account for a substantial proportion of familial cases, there are other genes yet to be discovered, particularly in patients with type 3 FTLD-TDP without a GRN mutation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas tau
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Demencia
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Péptidos y Proteínas de Señalización Intercelular
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Mutación
Límite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurology
Año:
2009
Tipo del documento:
Article
País de afiliación:
Reino Unido