A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.

Our results suggest that the frequency of Y chromosome AZF microdeletions is elevated in individuals with severe spermatogenic failure and that gr/gr deletions are not associated with spermatogenic failure.

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants.

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Background: The widespread use of antiretroviral agents and the growing occurrence of HIV-1 strains resistant to these drugs have given rise to serious concerns regarding the transmission of resistant viruses to newly infected persons, which may reduce the efficacy of a first-line antiretroviral therapy. Methodology: RNA was extracted from plasma samples of 98 treatment-naïve individuals with a plasma HIV RNA viral load of at least 1,000 copies/ml. Both protease (pr) and reverse transcriptase (rt) were amplified and sequenced using an automated sequencer. National Agency for AIDS Research (ANRS) and Stanford HIV database algorithms were used for interpretation of resistance data. Results: In the protease segment, various minor mutations were present in the majority of the sequenced samples with high frequencies. Only two major mutations, M46L and V82L, were separately found in three individuals of 71 (4.2%) with one carrying both mutations. In the reverse transcriptase gene, no NNRTIs-associated resistance mutations were detected. Only one patient of 70 (1.4%) carried the F77L mutation that is associated with NRTIs resistance. Genetic subtyping revealed that 74.6% of samples were infected with subtype B, 15.5% with CRF02_AG, 4.2% with CRF01_AE, 1.4% with C, 2.8% with G and 1.4% with subtype F2. Conclusions: The low prevalence of major mutations associated with resistance to antiretroviral drugs (ARVs) among drug-naïve individuals studied suggests that the routine of drug resistance testing may be unnecessary for all Moroccan individuals newly diagnosed or all patients beginning antiretroviral therapy. Nevertheless, continuous surveillance is required since greater access to antiretroviral drugs is expected in Morocco.

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3).AZFa and AZFc deletions were identified in men with severe spermatogenic failure at similar frequencies to those reported elsewhere. Gr/gr deletions were identified in case and control populations at 5.83% and 6.25% respectively suggesting that these deletions are not associated with spermatogenic failure. However, b2/b3 deletions were detected only in men with spermatogenic failure and not in the normospermic individuals. Combined with our previous data this shows an association of the b2/b3 deletion (p = 0.0318) with spermatogenic failure in some populations. We recommend screening for this deletion in men with unexplained spermatogenic failure.

Breast cancer (BC) is one of the most complex, diverse and leading cause of death in women worldwide. The present investigation aims to explore genes panel associated with BC in different African regions, and compare them to those studied worldwide.We extracted relevant information from 43 studies performed in Africa using the following criteria: case-control study, association between genetic variations and BC risk. Data were provided on mutations and polymorphisms associated with BC without fixing a specific date. Case-only studies and clinical trials were excluded.Our study revealed that the majority of African BC genetic studies remain restricted to the investigation of BRCA1 and BRCA2 genes and differences in their mutations spectrum. Therefore, it is necessary to encourage African researchers to characterize more genes involved in BC using methods generating global information such as next-generation sequencing in order to guide specific and more effective therapeutic strategies for the African community.