novel missense variation in ndufa9 gene in an iranian patient with fatal leigh syndrome

Mitochondrial diseases are caused by disturbances in the oxidative phosphorylation (oxphos) system. leigh syndrome encompasses a spectrum of mitochondrial diseases characterized by necrotizing encephalopathy. thus far, two cases carrying a variant in ndufa9 with a diagnosis of leigh syndrome have been reported. ndufa9 is a subunit involved in the assembly and stability of the mitochondrial respiratory complex i. we present a lethal phenotype of leigh syndrome in a four-month-old boy born to a consanguineous (first cousins) iranian couple. the patient’s clinical course was notable for episodes of cyanosis, seizures, lactic acidosis, nystagmus, spastic paraplegia, apnea, and respiratory arrest. due to high branched-chain amino acids, an initial diagnosis of maple syrup urine disease was considered; however, the patient did not respond to treatment. via exome sequencing, we identified a novel homozygous missense variation in ndufa9 (c.1069c>g, p.arg357gly), and a posthumous diagnosis of leigh syndrome was made. this report highlights the potential differential diagnosis of leigh syndrome and further describes the phenotypic spectrum of ndufa9 defects