Characterization of Novel POLG Mutations in Mitochondrial Encephalomyopathy: Pathogenic Validation and Comprehensive Genetic Profiling.

ABSTRACT:

Introduction/aims

Mitochondrial encephalomyopathies are multisystem disorders caused by defects in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) syndrome is a rare manifestation, often associated with POLG mutations. This study identifies a novel POLG mutation in a SANDO patient, validates its pathogenicity, and analyzes the molecular genetics of 61 reported POLG-SANDO cases.

Methods

After obtaining informed consent, the proband underwent neurological examination, electromyography, muscle/nerve biopsies (histochemical/ultrastructural analyses), and genetic testing (whole-exome sequencing, mtDNA analysis). Pathogenicity of identified POLG variants was assessed in Cas9-mediated primary neuronal models expre

SUBMITTER: Zhou F 

PROVIDER: S-EPMC12605960 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature