title: Mitochondrial DNA 11777C>A mutation associated Leigh syndrome: case report with a review of the previously described pedigrees.
abstract: Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesencephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespiratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50%) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encoding gene, which causes Arg --> Ser replacement. The mutation was also detected in low copy number in blood of mother. Albeit this mutation type is well recognized as a typical mtDNA mutation, according the reports available on the PubMed, this mutation was described only in four patients with wide phenotypic variations; here, we reviewed the characteristic clinical features of them. Taken together, the earliest onset of symptoms, the nature of the first presentation signs, the most rapid progression, the character of minor additional symptoms, and the early fatal outcome differentiate the phenotypic variant of the proband presented here from cases reported so far by others.
authors.affiliation: Department of Medical Genetics, University of Pecs, Pecs, Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Hadzsiev
authors.forename: Anita
authors.initials: A
authors.lastname: Maasz
authors.forename: Peter
authors.initials: P
authors.lastname: Kisfali
authors.forename: Endre
authors.initials: E
authors.lastname: Kalman
authors.forename: Eva
authors.initials: E
authors.lastname: Gomori
authors.forename: Endre
authors.initials: E
authors.lastname: Pal
authors.forename: Ervin
authors.initials: E
authors.lastname: Berenyi
authors.forename: Katalin
authors.initials: K
authors.lastname: Komlosi
authors.forename: Bela
authors.initials: B
authors.lastname: Melegh
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial