The wide POLG-related spectrum: An integrated view

International audience; The aims of this study were to describe the spectrum of recessively inherited POLG-related disorders, to report new POLG mutations and to discuss genotype-phenotype correlations in order to propose a strategy for diagnosis. Twenty eight patients diagnosed with two POLG mutations at 12 tertiary European centers of adult neurology were studied. Exhaustive phenotypic data, brain MRI, muscle analysis, mitochondrial DNA and POLG analysis findings were collected. Five distinct phenotypes were observed: Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoparesis (SANDO), autosomal recessive Progressive External Ophthalmoplegia (arPEO), Spino Cerebellar Ataxia with Epilepsy (SCAE), Mitochondrial Neuro Gastro Intestinal Encephalopathy (MNGIE)-like phenotype and Sensory Ataxic Neuropathy with Ophthalmoparesis but without dysarthria which we propose to name SANO. An increasing gradient of functional severity was appreciated from PEO with the best prognosis, to SANO, SANDO and finally SCAE respectively. Four new missense mutations were found. Regarding genotype/phenotype correlations, P587L mutation was associated with SANO rather than with SANDO (p