Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh‐like syndrome

Abstract

Leigh syndrome is the most common mitochondrial disorder in children characterized by necrotic lesions in the central nervous system. Both mitochondrial DNA (mtDNA) and nuclear DNA defects in the mitochondrial respiratory chain can lead to this disease. To characterize the clinical and genetic traits of Leigh or Leigh-like syndrome patients in China, 124 unrelated cases were collected between 1992 and 2005. Seventy-seven cases (62.1%) met the typical criteria of Leigh syndrome, including symmetrical bilateral abnormal signals in the basal ganglia, thalamus and brain stem, etc. Other cases (37.9%) belonged to Leigh-like syndrome with atypical clinical or radiological manifestations. Late-onset patients accounted for 20.2%, which is more than previously reported. Movement disorder was the most common symptoms in our patients. Thirty-two patients (25.8%) were confirmed to carry mutant genes. Among them, six cases (4.8%) have been demonstrated to have point mutations in mitochondrial DNA. Two separate patients were detected to have mutations on A8344G and A3243G. The T8993G point mutation was identified in one patient and T8993C in one other patient. SURF1 mutations associated with cytochrome-c oxidase deficiency were identified in 25 patients (20.2%). Four unreported variations have been identified in SURF1 gene from three patients. G604C was found in 22 patients. Only one patient had C214T mutation in the pyruvate dehydrogenase E1alpha subunit gene. In the remaining 92 patients (74.2%), a specific molecular dysfunction or underlying metabolic abnormality could not be identified.

Fatal breathing dysfunction in a mouse model of Leigh syndrome

“…We noted previously (23) that KO mice resemble humans with LS with regard to a large range of phenotypes and we now extend that to breathing. Respiratory abnormalities affect many LS patients (8,9,35,36) and virtually all patients with mutations in the NDUFS4 gene (16-21, 37); however, the link between mitochondrial dysfunction and breathing could not be investigated without an animal model.…”

SURF1 missense mutations promote a mild Leigh phenotype

“…Additionally, 11 LS patients, carriers of SURF1 missense mutations, reported in the literature were included in the analysis of natural history and clinical phenotype (15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Early Spinal Cord and Brainstem Involvement in Infantile Leigh Syndrome Possibly Caused by a Novel Variant

“…A wide range of mutations within the mitochondrial and nuclear genomes have been associated with functional defects of the enzyme systems involved in mitochondrial energy production including pyruvate dehydrogenase complex, cytochrome c oxidase (complex IV), adenosine triphosphatase (ATPase) 6 mutation (complex V), and complex I deficiency. [4][5][6] Clinical diagnosis is often accepted if there is a combination of appropriate clinical features, lactic acidosis, and typical neuroimaging findings.…”