Characterization and mRNA expression analysis of a novel ARG1 splicing mutation causing hyperargininemia

Area of Science:

• Genetics
• Biochemistry
• Molecular Biology

Background:

• Hyperargininemia is an autosomal recessive urea cycle disorder caused by biallelic mutations in the ARG1 gene.
• Splicing mutations in ARG1 are rare and may lead to more severe phenotypes compared to missense mutations.

Observation:

• A young patient with hyperargininemia was found to have a novel homozygous ARG1 IVS4-1G>C point mutation.
• Molecular analysis revealed a splicing defect, resulting in a mutated mRNA transcript that retained 51 base pairs from intron 4.

Findings:

• The identified ARG1 splicing mutation leads to aberrant mRNA with retained intronic sequences.
• Two previously undescribed alternatively spliced ARG1 transcripts, lacking exon 4 or exons 4 and 5, were identified in the patient and controls.

Implications:

• This study expands the known spectrum of ARG1 mutations associated with hyperargininemia.
• The findings highlight the importance of investigating splicing defects in urea cycle disorders and reveal novel ARG1 splicing variants.