Early onset dementia (encompassing fronto-temporal dementia and prion disease)Gene: SNCB
2 cases reported by Ohtake et al 2004. One sporadic and one familial but with reduced penetrance. Targeted sequencing of only 2 candidate genes. Functional studies of Psol et al 2021 suggest that the two variants identified cause neuropathological lesions.
PMID: 33760043 - Psol et al 2021 - expressed the V70M and P123H variants found by Ohtake et al 2004 using adeno-associated viral vectors in dopaminergic and non-dopaminergic neurons in vitro and in vivo. They found that both mutations cause distinct and mutually exclusive neuropathological lesions.
PMID: 15365127 - Ohtake et al 2004 - looked at 33 sporadic cases of dementia with Lewy bodies (DLB) and 10 kindreds segregating DLB and screened the alpha-synuclein and beta-synuclein genes for variants. 2 unrelated patients were found to have variants in the beta-synuclein gene (SNCB) - G208A:V70M (sporadic case) and C368A:P123H (familial case). 3 of the proband's cousins, all over age 70, in the familial case were screened for the P123H variant. 1 cousin who was heterozygous and 1 homozygous had possible signs of DLB. 1 heterozygous cousin age 80 had no signs of DLB. Authors suggest this is an autosomal dominant trait with reduced penetrance . The clinical description of the familial case was first described in PMID: 12641375 (Bonner et al 2003).
Created: 5 May 2021, 5:29 p.m. | Last Modified: 5 May 2021, 5:29 p.m.
Panel Version: 1.48
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dementia, Lewy body, OMIM:127750
SNCB was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease)panel. Sources: Radboud University Medical Center, Nijmegen