Human Genomics

Featured article: Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion

​​​​​​​Spataro et al. present the genetic profile of two patients with juvenile-onset ALS. They performed whole-exome sequencing, identifying candidate pathogenic mutations, and found that only ATP13A2 was found to harbor recessive changes associated with juvenile-onset ALS. They then used a zebrafish model to confirm the role of this gene in central and peripheral nervous system maintenance, corroborating the damaging direction of effect of the change detected. This expands the phenotypic spectrum associated with variants of this gene, which is associated with other neurodegenerative disorders, to also include juvenile-onset ALS. Their findings highlight the importance of establishing a complete genetic profile in order to obtain an accurate clinical diagnosis.