Adult onset neurodegenerative disorder

Gene: SNCB

I don't know

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, 5:30 p.m. | Last Modified: 5 May 2021, 5:30 p.m.

Panel Version: 2.174

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Dementia, Lewy body, OMIM:127750

Publications

• 33760043
• 15365127
• 12641375

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber

Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.

Panel Version: 1.106

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

I don't know

One report of two variants. Mouse model appears to support pathogenicity.

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
Unknown

Phenotypes
Dementia, Lewy body, 127750

Publications

• 15365127
• 21045828

Variants in this GENE are reported as part of current diagnostic practice