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

Autor:	Perrone E; Universidade Federal de São Paulo, Departamento de Genética Médica, São Paulo, SP, Brazil.; GeneOne, Dasa, São Paulo, SP, Brazil., Cavole TR; Universidade Federal de São Paulo, Departamento de Genética Médica, São Paulo, SP, Brazil., Oliveira MG; Universidade Federal de São Paulo, Departamento de Genética Médica, São Paulo, SP, Brazil., Virmond LDA; Universidade Federal de São Paulo, Departamento de Genética Médica, São Paulo, SP, Brazil., Silva MFB; Universidade Federal de São Paulo, Departamento de Genética Médica, São Paulo, SP, Brazil., Soares MFF; Universidade Federal de São Paulo, Departamento de Radiologia, São Paulo, SP, Brazil., Iglesias SBO; Universidade Federal de São Paulo, Departamento de Pediatria, São Paulo, SP, Brazil., Falconi A; GeneOne, Dasa, São Paulo, SP, Brazil., Silva JS; GeneOne, Dasa, São Paulo, SP, Brazil., Nakano V; GeneOne, Dasa, São Paulo, SP, Brazil., Milanezi MF; GeneOne, Dasa, São Paulo, SP, Brazil., Mendes CSC; Universidade Federal de São Paulo, Departamento de Pediatria, São Paulo, SP, Brazil., Curiati MA; Universidade Federal de São Paulo, Departamento de Pediatria, São Paulo, SP, Brazil., Micheletti C; Universidade Federal de São Paulo, Departamento de Pediatria, São Paulo, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Genetics and molecular biology [Genet Mol Biol] 2020 May 29; Vol. 43 (2), pp. e20180271. Date of Electronic Publication: 2020 May 29 (Print Publication: 2020).
DOI:	10.1590/1678-4685-GMB-2018-0271
Abstrakt:	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.
Databáze:	MEDLINE
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