Camptocormia as a Novel Phenotype in a Heterozygous POLG2 Mutation

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Mitochondrial dysfunction is central to neurodegenerative disorders.
• Nuclear-encoded proteins like DNA polymerase gamma (POLG and POLG2) are vital for mitochondrial DNA (mtDNA) replication.
• While POLG mutations frequently cause mitochondrial myopathies, POLG2 mutations are rarely described.

Purpose of the Study:

• To report a novel presentation of a POLG2 gene mutation.
• To expand the understanding of the phenotypic spectrum associated with POLG2 mutations.
• To highlight the diversity of mitochondrial disorders of nuclear origin.

Main Methods:

• Case study of a 68-year-old woman with a 20-year history of camptocormia, proximal weakness, and elevated creatine kinase.
• Muscle histology revealing COX-negative fibers.
• Next-generation sequencing identifying a heterozygous c.1192-8_1207dup24 mutation in the POLG2 gene.

Main Results:

• The patient presented with camptocormia as the predominant clinical feature.
• Genetic analysis confirmed a previously reported heterozygous mutation in the POLG2 gene.
• This represents the first documented case of a POLG2 mutation primarily manifesting as camptocormia.

Conclusions:

• POLG2 mutations can lead to mitochondrial disorders with camptocormia as the main phenotype.
• The phenotypic spectrum of POLG2-associated diseases is broader than previously recognized.
• This case underscores the wide variability in clinical presentations of nuclear-inherited mitochondrial disorders.