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Unlike adult cases reported so far, movement disorders dominated our patient's clinical picture and appeared as a tremor syndrome with childhood onset but significant progression in the fifth decade, with no identifiable triggers. 3-methylglutaconic aciduria type I (3-MGA-I) is a rare autosomal recessive disorder of leucine metabolism; since its description in 1976 [[12]] about 40 cases have been reported, mostly with a paediatric onset featuring intellectual disability, seizures and motor deficits [[13]]. In conclusion, our paper confirms the high variability of 3-MGA-I in adulthood and underlines the importance of considering inherited metabolic disorders, especially organic acidurias, in adult patients presenting with movement disorders and radiological findings consistent with extensive leukoencephalopathy. [Extracted from the article]

Neurofibromatosis type 1 (NF1) is caused by loss of function mutations of the NF1 gene, which are de novo in 50% of cases. Although this gene shows one of the highest mutation rates in the human genome, germline mosaicism is very rare in this condition. We describe the molecular analysis of a family in which neurofibromatosis type 1 occurred in two out of four siblings born to unaffected parents. Molecular analysis of the NF1 gene identified in both patients the same splicing mutation c.1392+ 1G>A, which was absent in parental lymphocytes. Microsatellite analysis showed that the two affected siblings shared the same maternal allele, however a specific PCR-RFLP assay excluded the presence of the NF1 splicing mutation in multiple maternal tissues. Our molecular and clinical findings are consistent with a germline mosaicism for the NF1 splicing mutation. This is the first case of maternal germline mosaicism for a NF1 mutation characterized so far at the molecular level. Our data confirm that germline mosaicism is rare in neurofibromatosis 1, but it has important implications for genetic counseling. [ABSTRACT FROM AUTHOR]