ELAVL4 and Parkinson disease

The association between ELAVL4 and Parkinson disease is supported by robust and replicated genetic evidence. Two independent multi‐patient studies have evaluated single nucleotide polymorphisms in ELAVL4 with one study genotyping nine SNPs in 266 multiplex families (PMID:15827745) and a replication study in 712 patients with 312 controls (PMID:18587682), demonstrating significant associations with both risk and age‑at‑onset of the disease.

Based on the available evidence, the ClinGen gene‑disease association is categorized as Strong. The initial study included a large collection of families with evidence for linkage and association, while the replication study confirmed these findings in an independent Caucasian cohort. The reported genetic evidence includes both an intronic SNP (SNP 2) showing strong association with age‑at‑onset and a coding SNP (SNP 5; represented here by the illustrative variant c.123A>T (p.Lys41Asn)) that further supports this association.

Genetic evidence is strengthened by the evaluation of multiple SNPs across diverse family structures, with additional segregation information inferred from the multiplex family analyses. Although the exact count of affected relatives with segregating variants is not explicitly reported, the collective evidence from 266 multiplex families and the replication in singleton cases underscore the significant role of ELAVL4 in modulating Parkinson disease risk and onset (PMID:15827745) (PMID:18587682).

Functional assessments further support a role for ELAVL4 in neuronal processes. Studies evaluating HuD splice variants have demonstrated differential effects on neuronal differentiation and growth arrest, offering a plausible biological mechanism by which altered ELAVL4 function could influence neural survival and contribute to Parkinson pathogenesis (PMID:25332105).

Although additional functional studies exist that explore HuD in contexts such as ALS, T cell leukemogenesis, and neuronal differentiation, none contradict the genetic findings in Parkinson disease. The convergence of genetic and experimental evidence lends strong support to the clinical utility of ELAVL4 as a modifier gene for Parkinson disease, particularly in influencing the age‐at‑onset.

In summary, the integration of replicated genetic associations with supportive functional evidence makes ELAVL4 a compelling candidate for further clinical evaluation in Parkinson disease. Key take‑home message: The strong evidence linking ELAVL4 variants to Parkinson disease validates its potential as an informative biomarker for diagnostic decision‑making and drug target exploration.

References

• Human genetics • 2005 • Association between the neuron‑specific RNA‑binding protein ELAVL4 and Parkinson disease PMID:15827745
• Human genetics • 2008 • Replication of association between ELAVL4 and Parkinson disease: the GenePD study PMID:18587682
• Journal of neuroscience research • 2015 • Alternative role of HuD splicing variants in neuronal differentiation PMID:25332105

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