Molekularna tipizacija tuniskih klonova vrste Myzus persicae (Hemiptera: Aphididae) pomoću mikrosatelitskih biljega

In order to assess the genetic differentiation among Tunisian clones belonging to the Myzus persicae complex (M. persicae (Sulzer), M. antirrhinii (Macchiati) and M. nicotianea Blackman), the molecular technique of microsatellites was used in this study. These markers offer sensitivity and are useful in population genetic studies of parthenogenetic organisms. Here, nine polymorphic microsatellite loci were amplified to distinguish between six parthenogenetic clones belonging to M. persicae complex collected from two different Tunisian areas. Interestingly, this technique allowed discrimination between five different genotypic classes among the six clones. Furthermore, analysis of genetic relatedness between the genotypic classes revealed that two Tunisian clones did not cluster either in M. persicae or in M. antirrhinii taxa, whereas, the four other Tunisian clones clustered into the M. persicae Sulzer taxa.U cilju utvrđivanja genetičkih razlika između tuniskih klonova kompleksa Myzus persicae (Sulzer), M. antirrhinii (Macchiati) i M. nicotianea (Blackman) upotrijebljena je molekularna mikrosatelitska tehnika. Ovi su biljezi vrlo osjetljivi i korisni u takvim istraživanjima partenogenetskih organizama. Umnoženo je devet polimorfnih lokusa mikrosatelita kako bi se razlikovalo šest partenogenetskih klonova kompleksa M. persicae sabranih u dva različita područja u Tunisu. Zanimljivo je da je ova tehnika omogućila razlikovanje između pet različitih genotipskih razreda tih šest klonova. Nadalje, analize genetičke srodnosti između genotipskih razreda pokazale su da dva tuniska klona nisu u istoj grupi niti s M. persicae, niti s M. antirrhinii, dok se četiri tuniska klona nalaze unutar vrste M. persicae Sulzer

201: Are QT intervals correlated to apnea-hypopnea index in obstructive sleep apnea?

IntroductionSeveral studies proved that obstructive sleep apnea (OSA) is associated with cardio-vascular diseases such as cardiac arrhythmia. QT duration and dispersion reflect the heterogeinity of ventricular repolarization and are considered as precursors of ventricular arrhythmiaAimThe aim of this study is to assess the relation between the severity of OSA parameters as apnea hypopnea index and QT intervals.MethodsForty patients (18 men and 22 women) who were diagnosed with OSA by overnight polysomnography were included in this prospective study. The mean age was 56±10 years old. They were all in sinus rhythm. Before initiating continuous positive airway pressure therapy, we calculated on a 12 lead ECG : QT duration (QTend) corrected to Bazett formula and QT dispersion (QT end max -QT end min).ResultsTwenty four patients had severe OSA (AHI >30), 4 had moderate OSA (AHI between 15 and 30) and 12 had a mild OSA (AHI between 5 and 15). There was a significant positive correlation between QT dispersion and AHI (r=0.48, p=0.001)ConclusionThe severity of OSA seems to be correlated with ventricular repolarization heterogeinity These results suggest that the higher is the AHI the higher is the risk of ventricular arrhythmia occurence. Further studies are needed to validate these results

Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives

International audienceObjectiveWe synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection‐enhanced delivery (CED) as a strategy for delivery.MethodsTo overcome the issue of their poor solubility, these ferrocenyl‐tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polymeric nanocapsules (PNL‐NC). We describe the chemistry, the encapsulation and the physicochemical characterization of these formulations.Key findingsStarting compounds [phthalimido‐ferrocidiphenol and succinimido‐ferrocidiphenol], esterified prodrugs and their nanocapsules formulations were characterized.These drug candidates displayed a strong in vitro activity against breast and glioblastoma cancer cells. The ester prodrugs were toxic for glioblastoma cells (IC50 = 9.2 × 10−2 μm and 6.7 × 10−2 μm, respectively). The IC50 values for breast cancer cells were higher for these compounds. The encapsulation of the esterified compounds in LNCs (≈50 nm) or PCL‐NCs (≈300 nm) did not prevent their efficacy on glioblastoma cells. These anticancer effects were due to both blockade in the S‐phase of the cell cycle and apoptosis. Moreover, the tamoxifen derivatives‐loaded nanocapsules induced no toxicity for healthy astrocytes and showed no haemolytic properties. Loaded Lipid Nanocapsules (LNCs) presented interesting profiles for the optimal delivery of active compounds.ConclusionsPhthalimido‐ and Succinimido‐esters represent an innovative approach to treat cancers with cerebral localizations such as glioblastoma or brain metastases from breast cancers

Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.

Usher syndrome (USH) is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3) are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys), in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24), and a nonsense mutation, c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss

A Tunisian family with a novel mutation in the gene CYP 4F22 for lamellar ichthyosis and co‐occurrence of hearing loss in a child due to mutation in the SLC 26A4 gene

International audienceBackground: Co-occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations.Methods: We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis-ichthyosis-deafness (KID) syndrome. WES was performed for the index case, and all members of the nuclear family were sequenced (Sanger method).Results: The WES approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 of SLC26A4 gene, associated with isolated HL and a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 of CYP4F22 gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale-Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the HL and ichthyosis, respectively.Conclusions: The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co-occurrence of two distinct clinical entities. In addition, in countries with limited resources, WES sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling

Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia

Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background