HS1BP3 – Essential Tremor

The genetic evidence for an association between HS1BP3 and essential tremor is mixed. One multi‐patient study identified a nucleotide change, re‐formatted here as c.828C>G (p.Ala265Gly), that segregated with essential tremor in 2 families, with 12 heterozygous carriers detected among patients with dominantly inherited essential tremor (PMID:16211613). This finding initially supported a role for HS1BP3 in the pathogenesis of essential tremor and highlighted a potential contribution to the disorder in familial cases.

However, further investigations have introduced significant conflicting evidence. In a subsequent family study, the same A265G variant was identified in 7 individuals but failed to cosegregate with essential tremor, Parkinson disease, or Bell’s palsy in a Mexican pedigree (PMID:17353387). Additionally, a case–control analysis specifically evaluating Parkinson disease found no association with the HS1BP3 variant (PMID:19524641), casting further doubt on its pathogenic relevance to essential tremor. Overall, the conflicting segregation data and lack of conclusive functional evidence lead to a disputed gene‑disease association.

Key take‑home sentence: Although initial reports implicated HS1BP3 in familial essential tremor, subsequent studies have failed to confirm its pathogenicity, emphasizing that its clinical utility remains uncertain and warrants further investigation.

References

• Movement disorders • 2006 • HS1-BP3 gene variant is common in familial essential tremor PMID:16211613
• Archives of neurology • 2007 • A family with Parkinson disease, essential tremor, bell palsy, and parkin mutations PMID:17353387
• Neuroscience letters • 2009 • DRD3 Ser9Gly and HS1BP3 Ala265Gly are not associated with Parkinson disease PMID:19524641

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