Fig. 4

Genotype and phenotype correlation according to the type of mitochondrial damage. DSBR is involved in neurodevelopmental impairment without mitochondrial involvement evidence (a), whereas neurodegenerative disorders proceed from SSBR deficiency or mitochondrial homeostasis dysfunction. In SSBR related diseases, the protein variants cause an indirect effect on mitochondria that lead to exclusively neurological impact characterized mainly by peripheral neuropathy and cerebellum atrophy (b). On the other hand, mutations associated with mitochondrial functioning itself have direct systemic implications (c). Although both clinical categories have mitochondrial involvement, DNA repair deficiency is the primary cause of neuropathological tropism (discussed later). MIRAS: mitochondrial recessive ataxia syndrome / MELAS: mitochondrial myopathy encephalopathy lactic acidosis and stroke