Ourstudy supports that the phenotype caused by C12orf65 genevariants is heterogeneous and varies from spastic paraparesis to Leigh syndrome.Loss-of-function variants are more likely to cause the disease, and variantsaffecting the GGQ domain tend to be associated with more severe phenotypes,reinforcing a possible genotype-phenotype correlation. Here, MTRFR is linked to Leigh syndrome.