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Two cases are reported of a boy and a girl with similar neurocutaneous syndromes clinically characterized by hyperpigmented skin patches and severe CNS involvement. The diagnosis of atypical cases of Incontinentia Pigmenti is suggested. The different syndromes with mental and motor retardation associated with skin abnormalities (Incontinentia Pigmenti, Ito's hypomelanosis, phakomatoses, etc.) are reviewed.

Large-scale deletions of mitochondrial DNA (mtDNA) have been described in patients with progressive external ophthalmoplegia (PEO) and ragged red fibers. We have determined the exact deletion breakpoint in 28 cases with PEO, including 12 patients already shown to harbor an identical deletion; the other patients had 16 different deletions. The deletions fell into two classes. In Class I (9 deletions; 71% of the patients), the deletion was flanked by perfect direct repeats, located (in normal mtDNA) at the edges of the deletion. In Class II (8 deletions; 29% of patients), the deletions were not flanked by any obviously unique repeat element, or they were flanked by repeat elements which were located imprecisely relative to the breakpoints. Computer analysis showed a correlation between the location of the deletion breakpoints and sequences in human mtDNA similar to the target sequence for Drosophila topoisomerase II. It is not known how these deletions originate, but both slipped mispairing and legitimate recombination could be mechanisms playing a major role in the generation of the large mtDNA deletions found in PEO.

We report an 8-year-old patient with clinical features suggesting Leigh's syndrome and with a decreased activity of the E1 component of the pyruvate dehydrogenase complex in cultured skin fibroblasts. A nerve biopsy showed the presence of severe peripheral neuropathy, rarely described in the literature. The partial correction of lactic acidosis with oral sodium bicarbonate chronic therapy may result in a slow evolution of the clinical symptoms.

Subunit VIII of mammalian cytochrome c oxidase (COX; EC 1.9.3.1) exists in at least two isoforms, because different but related polypeptides have been identified in COX isolated from liver and heart of both beef and pig. We have isolated a full length cDNA specifying subunit VIII of human COX from a human liver cDNA library. Sequences hybridizing to this cDNA are present at only one site, the COX8 locus, on human chromosome 11q12-q13. The deduced human polypeptide is 58% identical with COX VIII isolated from beef liver, but only 38% identical with COX VIII isolated from beef heart. Transcriptional analysis shows that an mRNA identical with the isolated cDNA is present in abundant amounts not only in human and monkey liver tissue, but in heart and skeletal muscle as well, tissues not known previously to contain this isoform. Since the only COX VIII subunit found in human heart agrees 100% with the polypeptide deduced from this coxVIII cDNA, it may well be that, in distinction to other mammals, only one form of COX VIII exists in primates.

We report a new case of MERRF (myoclonus epilepsy with ragged red fibers) syndrome with basal nuclei calcification on the brain CT scan, without hormonal abnormalities, with high CSF protein and hyperlactacidemia, juvenile onset and death at 18 years. Biochemical study of mitochondrial muscle enzymes showed decreased NADH-cytochrome-C-reductase and Succinate-cytochrome C-reductase activity, suggesting a Complex III defect of the respiratory chain. Similar reported cases are reviewed.