Chiari malformation type 1 with combined nuclear PAX1 and DKK1 genes and mitochondrial D-loop variants: a case report

Chiari malformation type 1 (CM 1) is a rare and complex neurological condition. This congenital condition affects the lower posterior fossa, where the brain connects to the spinal cord. Although the exact cause of CM 1 remains unclear, genetic predisposition plays a considerable role in structural defects of the cerebellum. Here, we report on a 15-year-old female patient with CM 1 who exhibited both nuclear and mitochondrial genetic variants, a combination that has not been previously described. We identified a silent mutation in exon 2 (c. 556 G>A, p. Lys185=) of PAX1 and a DKK1 variant in intron 3 (548-3 t>C) in the nuclear DNA. We also screened the D-loop region of mitochondrial DNA as it exhibits a higher susceptibility to mutations than other mitochondrial DNA regions. Several hotspot variants were revealed, including those in positions 303-309 and 16519 (t>C), as well as some variants that had not been documented in MITOMAP. Our findings highlight the potential role of genetic alterations in D-loop in CM 1.