Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12.

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.

Urinary tract infection with Corynebacterium aurimucosum after urethroplasty stricture of the urethra: a case report.

INTRODUCTION: Corynebacteria have an important place among the commensal flora of the skin and mucous membranes. Except for Corynebacterium diphtheriae, they were once considered contaminants of mucosa. Recent publications in medical bacteriology have highlighted the importance of several species, such as C. aurimucosum. To the best of our knowledge, we report the first isolation of this strain from urine. CASE PRESENTATION: We report a case of a patient with a urinary tract infection with C. aurimucosum. We isolated this bacterium from a 52-year-old man of Wolof ethniticity (an ethnic group in Senegal, West Africa) at the regional hospital of Saint Louis, Senegal. Microscopic examination of his total urine sample showed coryneform Gram-positive bacilli associated with a high leukocyte reaction. After repeated isolation of the corynebacteria in three samples from the patient's urine, it was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The strain was susceptible to antibiotics, except for penicillin and co-trimoxazole. The potential infectious role of these commensal species in several infections should be taken into consideration. CONCLUSIONS: This case highlights the significant proportion of species in the genus Corynebacterium other than dyphteriae in the infectious process. The use of mass spectrometry for identification highlights the originality of this work and the importance of these new diagnostic tools that are unavailable in most health facilities of countries with limited resources. We share the results of our method of identification of the isolated bacteria. This case should prompt attention to these rare bacteria, which can cause severe infections.

A candidate gene for autoimmune myasthenia gravis.

OBJECTIVE: We sought to identify a causative mutation in a previously reported kindred with parental consanguinity and 5 of 10 siblings with adult-onset autoimmune myasthenia gravis. METHODS: We performed genome-wide homozygosity mapping, and sequenced all known genes in the one region of extended homozygosity. Quantitative and allele-specific reverse transcriptase PCR (RT-PCR) were performed on a candidate gene to determine the RNA expression level in affected siblings and controls and the relative abundance of the wild-type and mutant alleles in a heterozygote. RESULTS: A region of shared homozygosity at chromosome 13q13.3-13q14.11 was found in 4 affected siblings and 1 unaffected sibling. A homozygous single nucleotide variant was found in the 3'-untranslated region of the ecto-NADH oxidase 1 gene (ENOX1). No other variants likely to be pathogenic were found in genes in this region or elsewhere. The ENOX1 sequence variant was not found in 764 controls. Quantitative RT-PCR showed that expression of ENOX1 decreased to about 20% of normal levels in lymphoblastoid cells from individuals homozygous for the variant and to about 50% in 2 unaffected heterozygotes. Allele-specific RT-PCR showed a 55%-60% reduction in the level of the variant transcript in heterozygous cells due to reduced mRNA stability. CONCLUSION: These results indicate that this sequence variant in ENOX1 may contribute to the familial autoimmune myasthenia in these patients.