Weak association of pathogenic <i>ERBB4</i> variants with amyotrophic lateral sclerosis

However, gene burden analyses did not find an enrichment of rare variants in patients, leaving the pathogenic role of ERBB4 in ALS unclear. Therefore, this study aimed to reassess the association of ERBB4 variants with ALS.</p> <p>Next-generation sequencing was performed in 250 ALS and 714 non-ALS patients.

Low-frequency, deleterious non-synonymous ERBB4 variants were filtered, and their allele frequencies were compared between groups.</p> <p>In total, 42 low-frequency and deleterious ERBB4 variants were identified in patients and normal controls, with three variants in all groups. There was no significant difference in allele frequencies between ALS and non-ALS groups. Additionally, four reported pathogenic variants (c.158A > G, c.284G > A, c.965T > A, and c.1624G > A) were observed in patients with neuromuscular disease or leukoencephalopathy, as well as normal controls.