Researchers have found a novel mutation in the mitochondrial gene MT-TL2 in two siblings with Leigh syndrome, according to a new study published in the journal Neurology Genetics.
Leigh syndrome, usually apparent in babies before age 1, is a rare genetic neurometabolic disorder associated with mutations in mitochondrial and nuclear DNA. Clinical manifestations include progressive loss of movement, seizures, hypotonia(lack of muscle tone), dystonia (uncontrollable and painful muscle contractions), gait disturbance, respiratory failure. Patients also have neurodegenerative lesions in one or more brain regions, including the basal ganglia, thalamus, brainstem, and cerebellum.
The African-American siblings, a boy and a girl, had different outcomes according to the study “Novel Mutation In Mitochondrial DNA In 2 Siblings With Leigh Syndrome.”
The brother had motor development delays since age 1 year and progressive movement difficulties and weakness by age 2. He was not able to walk or pull himself up to stand without support. The boy developed respiratory failure and died at age 3 1/2. His younger sister showed motor regression, speech delay, and ataxia, and lost the ability to walk or stand without support. She was able to crawl and sit with help and by age 4 age she was reported to be neurologically stable.
Analysis of the siblings’ mitochondrial DNA revealed the mutation in the gene MT-TL2. The gene encodes the protein rRNA that plays a crucial role in protein synthesis. The same mutation was also identified in their mother who displayed no neurological symptoms but had bipolar disease.
Although MT-TL2 mutations have been reported in patients with mitochondrial encephalomyopathy and myopathy, the association between this exact mutation and Leigh syndrome has not been clearly described.
“We speculate that this mutation in the highly conserved region [of the gene] is associated with Leigh syndrome phenotypes in our patients,” the authors wrote. “This is supported by the presence of the same MT-TL2 mutation in their mother with bipolar disorder, indicating that this change may have variable penetrance or heterogeneous expressivity commonly seen with other mitochondrial disorders. We suggest that patients with clinical criteria of Leigh syndrome be screened for this mutation to confirm such an association.”