A case report on a novel MT-ATP6 gene variation in atypical mitochondrial Leigh syndrome associated with bilateral basal ganglia calcifications.

Leigh Syndrome (LS) is a rare, hereditary progressive neurodegenerative disorder of infancy or early childhood associated with a highly variable clinical presentation even among siblings. Further, genetic heterogeneity makes its diagnosis complicated. Its causative genetic variations are notified in some of the mitochondrial and nuclear genes. Here, we report an atypical case of LS in a 9-year-old boy associated with a novel variation in MT-ATP6 gene. The atypical findings were Bilateral Basal Ganglia Calcification (BGC) and late survival age in the patient. Analyses of the Whole Mitochondrial Genome Sequencing (WMGS) results of the recruited patient and his mother at different read coverage, first at 100× and later repeated at 500×, revealed a novel disease-associated variation in the already known disease-associated MT-ATP6 gene. In conclusion, the present study indicates amalgamation of both neuro-imaging and Next Generation Sequencing (NGS) Technologies aiding the proper diagnosis of LS in atypical cases. • 9-year-old boy presented with neurological complaints. • Finally diagnosed with atypical mitochondrial form of Leigh syndrome after clinical, radiological and genetic screening. • The atypical findings in the patient were his survival age and observation of dense bilateral signal abnormalities indicating calcification in the caudate nuclei on his brain CT. • Whole mitochondrial genome sequencing revealed a novel heteroplasmic mitochondrial variation m.8936T>A in MT-ATP6 gene in both patient and his mother but with different allele counts. A higher variation load of m.8936T>A variation in the patient than his mother can be concluded as disease-causing. • This case report emphasises the use of both neuro-imaging and Next Generation Sequencing (NGS) Technologies for the proper diagnosis of LS in atypical cases. [ABSTRACT FROM AUTHOR]