HAPLN4 – Essential Tremor

HAPLN4 has been implicated as a candidate gene for familial early‑onset essential tremor (ET) in multi‑patient exome sequencing studies. In one study of 37 ET families with an autosomal‑dominant inheritance pattern, HAPLN4 was identified among several candidate genes harboring potentially deleterious variants, although no specific variant details or extensive segregation data were provided (PMID:26508575). This study used predicted functional impact to shortlist candidate genes, thereby suggesting a possible contributory role for HAPLN4 in the disease process. A subsequent investigation expanded the candidate gene list in ET by including HAPLN4 along with other genes; however, these findings were based solely on exome‐analysis without additional experimental validation (PMID:34072005). The lack of detailed variant information and corroborative functional assays limits the genetic evidence available for HAPLN4, even though its repeated identification across independent studies adds some weight to its candidacy.

Overall, the current evidence supports only a limited association between HAPLN4 and essential tremor. While the data suggest that HAPLN4 may play a role in ET pathogenesis, the absence of clear segregation evidence, definitive variant characterization, and functional confirmation underscores the need for further research. Clinically, this candidate gene status could inform future diagnostic decision‑making and commercial gene panel development, but its utility for current clinical testing remains preliminary. Key take‑home: Although promising, HAPLN4 requires additional genetic and functional validation before it can be reliably integrated into essential tremor diagnostics.

References

• European Journal of Human Genetics • 2016 • Identification of candidate genes for familial early‑onset essential tremor PMID:26508575
• Pharmaceuticals (Basel, Switzerland) • 2021 • Genomic Markers for Essential Tremor PMID:34072005

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