Biallelic protein truncating EXOSC6 variants cause a neurodevelopmental disorder with cerebellar atrophy, ataxia, and global developmental delay

The article describes a patient with cerebellar atrophy, ataxia, and global developmental delay in whom two variants of the EXOSC6 gene were identified using exome sequencing. EXOSC6 is one of nine subunits of the RNA exosome complex, which plays an important role in RNA processing in cells. The maternal allele contains a deletion that removes 4 amino acids, while the paternal allele introduces a stop codon that removes the last 16 amino acids of the EXOSC6 protein. Functional analyses in yeast suggest that both variants are damaging and may affect protein stability. This case expands the spectrum of variants associated with exosomopathies, as previous patients had only single amino acid changes.