A de novo novel variant in the MT‐TD gene is associated with prominent extra‐neurologic manifestations

Abstract

AbstractDefects in the mitochondrial tRNA genes cause a group of highly clinically and genetically heterogeneous disorders, which poses a challenge for clinical identification and genetic diagnosis. Here, we present a pre‐school boy with a novel MT‐TD variant m.7560T>C at the heteroplasmy level of 76.53% in blood, 93.34% in urine sediments, and absent in the healthy mother's blood and urine. Besides convulsions, brain magnetic resonance imaging abnormalities and high plasma lactate, the boy presented with the prominent extra‐neurologic phenotype including steroid‐resistant nephrotic syndrome associated with focal segmental glomerulosclerosis characterized by abnormal mitochondria in podocytes, cortical blindness, and pancreatitis. To our knowledge, this is the unique case with MT‐TD m.7560T>C‐related multi‐organ impairments, which expands the phenotypic and mutational spectrum of primary mitochondrial diseases.