Novel heterozygous variant of ADPRHL2 causes pathogenic variation in CONDSIAS

Abstract

Adprhl2 (OMIM: 610624) mutation associated stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS, OMIM: 618170) is a sporadic neurodegenerative disease with poor prognosis. ADPRHL2 encodes ADP-ribosylhydrolase 3 (ARH3), which participates in ADP-ribosylation to remove poly-ADP ribose (PAR). We found a new compound heterozygous mutation in the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A in a 30-month-old boy, who showed gait instability, abnormal EEG, and developmental delay after respiratory infection. He died of convulsions 4 months after onset. By constructing a mutant plasmid and using Western blot to detect the expression of ARH3 and PAR, it was demonstrated that the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A is pathogenic according to ACMG guidelines.

Keywords

• ADPRRHL2
• CONDSIAS
• ARH3
• PAR