Novel NARS2 variant causing leigh syndrome with normal lactate levels

Area of Science:

• Genetics
• Mitochondrial Biology
• Neurology

Background:

• Leigh syndrome is a severe neurological disorder with diverse genetic causes.
• Diagnosis can be challenging due to variable clinical presentations and normal initial metabolic screening.
• Mitochondrial diseases are a significant group of inherited metabolic disorders.

Purpose of the Study:

• To report a case of Leigh syndrome diagnosed via whole-exome sequencing.
• To highlight the utility of genetic testing in complex cases of mitochondrial disease.
• To identify novel variants in genes associated with Leigh syndrome.

Main Methods:

• Clinical presentation and metabolic screening of a patient with suspected Leigh syndrome.
• Whole-exome sequencing (WES) for comprehensive genetic analysis.
• Bioinformatic analysis to identify pathogenic variants in disease-associated genes.

Main Results:

• Initial metabolic screening results were normal, delaying diagnosis.
• Whole-exome sequencing identified biallelic pathogenic variants in NARS2.
• One of the identified NARS2 variants was novel, expanding the known mutation spectrum.

Conclusions:

• Genetic testing, particularly WES, is crucial for diagnosing Leigh syndrome when metabolic screening is inconclusive.
• Mutations in NARS2 are a cause of Leigh syndrome, emphasizing its genetic heterogeneity.
• Early and accurate genetic diagnosis is essential for patient management and genetic counseling.