Congenital afibrinogenemia is a rare autosomal recessive coagulation disorder characterized essentially by bleeding symptoms, but miscarriages and, paradoxically, thromboembolic events can also occur. Most reported mutations leading to congenital afibrinogenemia are located in FGA encoding the fibrinogen A α-chain. In this study, we analysed 12 individuals from a consanguineous Syrian family with reduced or absent fibrinogen levels: those with fibrinogen levels around 1 g/l (n = 7) were found to be heterozygous for a novel frameshift mutation in FGA exon 5 (c.1846 del A) and those with undetectable fibrinogen levels (n = 5) were homozygous for the same mutation. This novel frameshift mutation is the most C-terminal causative FGA mutation identified to date in afibrinogenemic patients. The resulting aberrant Aα-chain (p.Thr616HisfsX32) is most likely synthesized, but is less efficiently assembled and/or secreted into the circulation given the phenotype of asymptomatic hypofibrinogenemia in heterozygous individuals and bleeding diathesis in homozygous individuals.

Objective: Activating mutations of the fms-like tyrosine kinase 3 gene ( FLT3 ) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3 /ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3 -ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3 -ITD mutation is considered as an independent poor prognostic factor in AML. Methods: FLT3 -ITD and FLT3 -KTD were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism- PCR (RFLP-PCR) in 44 adults AML patients with cytogenetically normal karyotype (AML-CN) at diagnosis to characterize FLT3 status. The results were correlated with the prognostic factors. Results: In this study, FLT3 -ITD mutations were identified in 7 (15.9%) of the 44 AML-CN patients. Among the 7 patients with FLT3 /ITD mutations, 6 patients revealed a typical ITDs mutation (fragment size was 329 bp) and one patient showed untypical ITD mutation (fragment size was ~400 bp). Whereas 37 patients (61.7%) were FLT3 -ITD. None of all AML-CN patients examined showed FLT3 -KTD mutations. Conclusions: Our results support that FLT3 -ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis. We concluded, FLT3 mutation analysis should be performed as a routine test in AML-CN patients.

Nucleophosphomin (NPM1) is a nucleocytoplasmic shuttling protein that plays an active role in ribosomal protein assembly, chromatin remodeling, DNA repair, replication, and transcription (Lindstrom 2011). Mutations in the NPM1 gene have been reported in 25-35% of

Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

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Celiac disease (CD) is a disorder caused by an aberrant autoimmune response to gluten ingestion in genetically susceptible individuals. Its prevalence nears 1%, and it is not considered typical in the Middle East because of the lack of reports in the Arabic countries. Therefore, this study aimed to define the prevalence of celiac disease in the Syrian community. Healthy young adults and volunteers ranging between 5–65-year-old were tested from December 2018 till May 2019. Samples from the participant's sera were tested for anti-tissue transglutaminase antibody (tTG) IgA/IgG by ELISA using the human recombinant transglutaminase antigen. One hundred participants with a mean ± SD of 22 ± 14 years-old were recruited in the study. Only one participant was suspected of having celiac disease. The mean ± SD of anti-tTG IgA/IgG values were 9.81 ± 9.61 for IgA and 6.64 ± 6.60 for IgG. The study shows no significant difference in IgA or IgG titers between males and females at P = 0.7, P = 0.8, respectively. The estimation of seroprevalence of CD antibodies in a healthy Syrian population is close to 1%. We suggest that the underdiagnosed CD might pose a high risk in Syria, contrary to previous thoughts.

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