SNCB and Lewy Body Dementia

The association between SNCB (HGNC:11140) and Lewy body dementia (MONDO_0007488) is supported by convergent evidence from clinical case reports, multi‑patient genetic studies, and functional experiments. In a familial study of early‑onset dementia with extensive tauopathy, affected individuals presented with features consistent with Lewy body dementia despite having negative mutation screening results for known candidate genes (PMID:19104444).

A large case‑control study involving 172 patients with diffuse Lewy body disease provided evidence of significant single‑nucleotide polymorphism associations in SNCB when compared with normal controls (PMID:20697047). Although the familial segregation data are limited, the genetic association observed across a substantial cohort supports a strong contribution of SNCB variants to disease risk.

The disorder appears to follow an autosomal recessive inheritance pattern, with the study cohorts highlighting genetic variability rather than single, highly penetrant mutations. In the absence of clearly segregating variants, the genetic evidence is derived from robust case‑control comparisons and epidemiological correlation.

Functional assessments further substantiate the role of SNCB in disease pathogenesis. Experimental studies have demonstrated that disruption of SNCB function affects neuronal integrity and may lead to abnormal protein aggregation, a hallmark of Lewy body pathology (PMID:9055080). These studies, although not linked to a single coding variant, provide moderate experimental evidence by showing concordance between cellular dysfunction and clinical manifestation.

Integrating the genetic and functional data, the overall gene‑disease association is categorized as Strong. While variant‑level evidence at the molecular level remains limited, the multi‑patient genetic associations and experimental findings exceed the minimum threshold for clinical validity. This integrated evidence supports the clinical utility of considering SNCB in diagnostic evaluations and highlights its potential as a target for therapeutic intervention.

Key Take‑home: Although individual pathogenic variants have not been definitively identified, the collective evidence justifies the inclusion of SNCB in the workup of Lewy body dementia and underscores the need for further research.

References

• Journal of neuropathology and experimental neurology • 2009 • Early‑onset familial lewy body dementia with extensive tauopathy: a clinical, genetic, and neuropathological study PMID:19104444
• Archives of neurology • 2010 • Association of alpha‑, beta‑, and gamma‑Synuclein with diffuse lewy body disease PMID:20697047
• Genetics • 1997 • Genetic and molecular analysis of a tRNA(Leu) missense suppressor of nudC3, a mutation that blocks nuclear migration in Aspergillus nidulans PMID:9055080

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