Leigh syndrome in a patient with a novel C12orf65 pathogenic variant: case report and literature review

• Published in: Genetics and molecular biology Vol. 43; no. 2; p. e20180271
• Main Authors: Perrone, Eduardo, Cavole, Thiago R., Oliveira, Manuella G., Virmond, Luiza do A., Silva, Marina de França B., Soares, Maria de Fatima F., Iglesias, Simone Brasil de O., Falconi, Ariane, Silva, Juliana S., Nakano, Viviane, Milanezi, Maria Fernanda, Mendes, Carmen Silvia C., Curiati, Marco Antonio, Micheletti, Cecília
• Format: Journal Article
• Language: English
• Published: Sociedade Brasileira de Genética 01.01.2020
• Subjects: BIOCHEMISTRY & MOLECULAR BIOLOGY; c12orf65; coxpd7; GENETICS & HEREDITY; Human and Medical Genetics; leigh syndrome; mitochondrial; oxidative phosphorylation; COXPD7; Leigh syndrome; mitochondrial; C12orf65; oxidative phosphorylation
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-gmb-2018-0271

Leigh syndrome is an early onset progressive disorder caused by defects in mitochondrial oxidative phosphorylation. Pathogenic variants in nuclear and mitochondrial genes are associated with the syndrome. Homozygous pathogenic variants in the C12orf65 gene impair the mitochondrial oxidative phosphorylation system. We describe a new case of Leigh syndrome caused by a novel pathogenic variant of the C12orf65 gene resulting in the lack of the Gly-Gly-Gln (GGQ) domain in the predicted protein, and review clinical and molecular data from previously reported patients. Our study supports that the phenotype caused by C12orf65 gene variants is heterogeneous and varies from spastic paraparesis to Leigh syndrome. Loss-of-function variants are more likely to cause the disease, and variants affecting the GGQ domain tend to be associated with more severe phenotypes, reinforcing a possible genotype-phenotype correlation.