Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase.

Helicase proteins are known to use the energy of ATP to unwind nucleic acids and to remodel protein-nucleic acid complexes. They are involved in almost every aspect of DNA and RNA metabolisms and participate in numerous repair mechanisms that maintain cellular integrity. The archaeal Lhr-type proteins are SF2 helicases that are mostly uncharacterized. They have been proposed to be DNA helicases that act in DNA recombination and repair processes in Sulfolobales and Methanothermobacter. In Thermococcales, a protein annotated as an Lhr2 protein was found in the network of proteins involved in RNA metabolism. To investigate this, we performed in-depth phylogenomic analyses to report the classification and taxonomic distribution of Lhr-type proteins in Archaea, and to better understand their relationship with bacterial Lhr. Furthermore, with the goal of envisioning the role(s) of aLhr2 in Thermococcales cells, we deciphered the enzymatic activities of aLhr2 from Thermococcus barophilus (Tbar). We showed that Tbar-aLhr2 is a DNA/RNA helicase with a significant annealing activity that is involved in processes dependent on DNA and RNA transactions.

Novel pleiotropic BRCA2 pathogenic variants in Lebanese families.

BRCA1 and BRCA2 associated pathogenic variants are the major cause of familial cases of early onset breast and ovarian cancers. Here we report two novel heterozygous pathogenic variants in exons 18 and 11 of the BRCA2 gene in two Lebanese families. The double nucleotide insertion c.8052_8053dupAA was identified in a 38-year-old Lebanese woman diagnosed with a breast cancer. The patient had a family history of affected first degree relatives. The double nucleotide deletion c.4342_4343delAA was identified in a 67-year-old woman with ovarian cancer. The patient came from a family marked by the occurrence of variable cancers. Her two daughters were also found to carry the deleterious variant. Both genetic aberrations result in a framing error that leads to a premature stop codon giving rise to unstable or truncated proteins. We further discuss two non-mutually exclusive potential scenarios related to the resulting haploinsufficiency and variant-specific dominant negative phenotype that might explain, at least in part, the variable expressivity associated with BRCA2 pathogenic variants.

A nationwide non-interventional epidemiological data registry on myelodysplastic syndromes in Lebanon.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral blood cytopenias, blood cells dysplasia, and increased risk for progression to acute leukemia.Physicians should be vigilant in diagnosing MDS and should be aware of the contemporary therapies that are always in progress. Most of the data on MDS epidemiology and management comes from developed countries. The incidence and features of MDS in the Arab countries, among them Lebanon, are not known. We undertook a nationwide epidemiological registry study of all newly diagnosed MDS cases through 2010-2011. Patients were referred by 21 hematologists/oncologists practicing in 17 hospitals and medical centers distributed across the entire country. 58 patients (29 males and 29 females) with confirmed MDS were included. The calculated incidence rate of MDS was 0.71 per 100,000 people. The median age at diagnosis was 73 years (range 16-86). The most common complaints on presentation were fatigue (70.7%), weakness (60.3%) and pallor (43.1%). Most patients were diagnosed as refractory anemia with excess blasts (RAEB; 36.2%) and refractory cytopenia with multilineage dysplasia (RCMD; 32.8%). This paper constitutes the first epidemiological report on the incidence and specific subtypes of MDS in Lebanon.

A collaborative nationwide lymphoma study in Lebanon: incidence of various subtypes and analysis of associations with viruses.

Incidence of various Hodgkin (HL) and non-Hodgkin lymphoma (NHL) subtypes and association with viruses in Lebanon are not known. We undertook a nationwide study of 272 patients diagnosed with lymphoma in 2007. HL comprised 32.7 % (n = 89) of cases while NHL represented 67.3 % (n = 183). Consistent with the literature, nodular sclerosis was the most predominant HL subtype (n = 57/89). Among NHL, B-cell NHL represented 88 % (n = 161/183), T-cell NHL 9 % (n = 17/183), whereas in 2.7 % it was not classifiable. The B-cell NHL comprised predominantly diffuse large B-cell lymphoma (46 %) and follicular lymphoma (23 %). 81 cases were reviewed by a panel of pathologists with 87.6 % concordance rate. Serology was negative for hepatitis C in 122 tested cases. HIV was positive in 2 cases. Two adult T-cell leukemia/lymphoma were HTLV-I positive. EBV IgG were positive in 88.5 % of cases. 38 EBV seropositive cases [27 NHL (24 B-cell, 3 T-cell) and 11 HL] were studied for EBV genome expression using EBV-encoded RNA (EBER)-in situ hybridization. EBER expression was positive in 8 (21 %) cases (6 HL, 2 T-cell NHL). The distribution of lymphoma subtypes in Lebanon appears similar to that of Western countries. The high rate of EBV positivity in HL and T-cell lymphoma by EBER deserves further investigation.