Leigh Syndrome Caused by a Novel Gene Variant in NDUFS8

Background: Leigh syndrome is a mitochondriopathy which can be inherited in an autosomal-recessive or X-linked-recessive manner, and also by mutated mitochondrial DNA. More and more new genetic defects are identified nowadays in the nuclear DNA, causing deficiency of the respiratory chain. A new gene defect is described below.

Methods: The case of a 5-year-old boy suffering clinically from Leigh syndrome is presented in the following. He showed increasing and variable tetra-spastics, atactic motion disorder, and a slight general development disorder. Both increasing and decreasing structural changes of basal ganglia were remarkable in MR imaging. A muscle biopsy and the genetic examination were initiated.

Results: The missense variant c.441G>C, p. (Met147lle) in the NDUFS8 gene was identified and confirmed by the trio-exome sequencing of both the patient and his consanguineous parents and by sanger sequencing of the patient. NDUFS8 encodes a subunit of the mitochondrial complex S1. Due to this gene variant, the exchange of a highly conserved amino acid can be predicted. Muscle biopsy showed a reduction in complex 1 activity of respiratory chain.

Conclusion: A new genetic defect was found which is probably responsible for the patient’s symptoms. A homozygous form of this genetic variant and the corresponding phenotype have not been described in the literature until now. Studies or the identification of variants in other patients are missing so far.