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Background Minocycline is an old tetracycline antibiotic that has shown antiinflammatory and antiapoptotic properties in different neurological disease mouse models. Previous single arm study in humans demonstrated benefits in individuals with Angelman Syndrome (AS); however, its efficacy in patients with Angelman Syndrome has not been assessed in a controlled trial. This was a randomized, double-blind, placebo-controlled, crossover trial in individuals with AS, aged 6 years to 30 years (n = 32, mean age 12 [SD 6·29] years). Participants were randomized to minocycline or placebo for 8 weeks and then switched to the other treatment (a subset of 22 patients) or to receive minocycline for up to 16 weeks (10 patients). After week 16, all patients entered a wash-out 8-week follow-up period. Results Thirty-six subjects were screened and 34 were randomized. Thirty two subjects (94·1%) completed at least the first period and all of them completed the full trial. Intention-to-treat analysis demonstrated the lack of significantly greater improvements in the primary outcome, mean changes in age equivalent of the development index of the Merrill-Palmer Revised Scale after minocycline compared with placebo (1·90 ± 3·16 and 2·00 ± 3·28, respectively, p = 0·937). Longer treatment duration up to 16 weeks did not result in better treatment outcomes (1·86 ± 3·35 for 8 weeks treatment vs 1·20 ± 5·53 for 16 weeks treatment, p = 0·667). Side effects were not significantly different during minocycline and placebo treatments. No serious adverse events occurred on minocycline. Conclusions Minocycline treatment for up to 16 weeks in children and young adults with AS resulted in lack of significant improvements in development indexes compared to placebo treatment. Treatment with minocycline appears safe and well tolerated; even if it cannot be completely ruled out that longer trials might be required for a potential minocycline effect to be expressed, available results and lack of knowledge on the actual mechanism of action do not support this hypothesis. Trial registration European Clinical Trial database (EudraCT 2013-002154-67), registered 16th September 2013; US Clinical trials database (NCT02056665), registered 6th February 2014. Electronic supplementary material The online version of this article (10.1186/s13023-018-0891-6) contains supplementary material, which is available to authorized users.

Mutations in BCS1L, a respiratory chain complex III assembly chaperone, constitute a major cause of mitochondrial complex III deficiency and are associated with GRACILE and Bjornstad syndromes. Here we describe a 4-year-old infant with hyperlactacidemia, mild liver dysfunction, hypotonia, growth and psychomotor retardation, dysmorphic features and mitochondrial complex III deficiency. Respiratory chain enzyme activities showed an isolated complex III defect in muscle and fibroblasts. Sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis revealed a novel homozygous BCS1L mutation, c.148A>G, which caused a p.T50A substitution at an evolutionarily conserved BCS1L region. The severity of the complex III enzyme defect correlated with decreased amounts of BCS1L and respiratory chain complex III in the affected tissues. Our findings support a pathogenic role for the novel BCS1L mutation in a patient with a singular clinical phenotype.