# Adult Leigh Syndrome Associated with the m.15635T>C Mitochondrial DNA Variant Affecting the Cytochrome b (MT-CYB) Gene

## TL;DR

A rare mitochondrial DNA variant is linked to a severe neurological disorder in an adult, causing multiple health issues.

## Contribution

The m.15635T>C variant in MT-CYB is confirmed as pathogenic in a new clinical context of adult Leigh syndrome.

## Key findings

- The m.15635T>C variant in MT-CYB is associated with complex III respiratory chain impairment.
- The variant was found in a haplogroup K1c1a background with additional non-synonymous polymorphisms.
- The variant was previously reported in a fatal neonatal case, suggesting a spectrum of disease severity.

## Abstract

We report on a sporadic patient suffering Leigh syndrome characterized by bilateral lesions in the lenticular nuclei and spastic dystonia, intellectual disability, sensorineural deafness, hypertrophic cardiomyopathy, exercise intolerance, and retinitis pigmentosa. Complete sequencing of mitochondrial DNA revealed the heteroplasmic nucleotide change m.15635T>C affecting a highly conserved amino acid position (p.Ser297Pro) in the cytochrome b (MT-CYB) gene on a haplogroup K1c1a background, which includes a set of four non-synonymous polymorphisms also present in the same gene. Biochemical studies documented respiratory chain impairment due to complex III defect. This variant fulfils the criteria for being pathogenic and was previously reported in a sporadic case of fatal neonatal polyvisceral failure.