Syndactyly is a condition well documented in current literature due to it being the most common congenital hand defect, with a large aesthetic and functional significance.There are currently nine types of phenotypically diverse non-syndromic syndactyly, an increase since the original classification by Temtamy and McKusick(1978). Non-syndromic syndactyly is inherited as an autosomal dominant trait, although the more severe presenting types and sub types appear to have autosomal recessive and in some cases X-linked hereditary.Gene research has found that these phenotypes appear to not only be one gene specific, although having individual localised loci, but dependant on a wide range of genes and subsequent signalling pathways involved in limb formation. The principal genes so far defined to be involved in congenital syndactyly concern mainly the Zone of Polarizing Activity and Shh pathway.Research into the individual phenotypes appears to complicate classification as new genes are found both linked, and not linked, to each malformation. Consequently anatomical, phenotypical and genotypical classifications can be used, but are variable in significance, depending on the audience.Currently, management is surgical, with a technique unchanged for several decades, although future development will hopefully bring alternatives in both earlier diagnosis and gene manipulation for therapy.

BACKGROUNDThe goals of the current study were to examine the incidence and severity of toxicity resulting from dexamethasone and prednisone during induction therapy for children with precursor B‐cell acute lymphoblastic leukemia (ALL) and to determine whether the addition of daunomycin affected toxicity.METHODSMedical records of patients with precursor B‐cell ALL from January 1996 through June 2000 were reviewed retrospectively for toxicity during the 4‐week induction phase and the 2 weeks after the induction phase.RESULTSOne hundred seventy‐six patients age < 14 years were diagnosed with precursor B‐cell ALL from January 1996 through June 2000. Of the 156 evaluable patients, 106 were treated with prednisone and 50 with dexamethasone. Fifty‐two patients received steroids, L‐asparaginase, and vincristine, whereas 104 high‐risk patients received daunomycin in addition to these 3 agents. The incidence of gastritis was significantly higher among patients receiving dexamethasone (P = 0.01); incidence rates of hyperglycemia, hypertension, and myopathy were similar for all treatment groups. Dexamethasone led to more weight gain than did prednisone (+11.9% vs. +5.4%; P = 0.002). Serious infections were observed in 27 (25.5%) and 18 (36%) patients receiving prednisone and dexamethasone, respectively (P ≤ 0.2). Five patients, four of whom received prednisone and one of whom received dexamethasone, died of infection. The addition of daunomycin to treatment regimens increased overall toxicity (P < 0.01). When daunomycin was included in treatment regimens, toxicity was greater among patients receiving dexamethasone; in contrast, when daunomycin was not included, toxicity was equal for both treatment groups. Regardless of daunomycin use, there was no difference in the incidence of serious infection between the two groups. ALL treatment was not compromised by steroid‐related toxicity in either group.CONCLUSIONSThe addition of daunomycin led to a much larger increase in dexamethasone‐related toxicity compared with the increase in prednisone‐related toxicity. Although the use of daunomycin enhanced dexamethasone‐related toxicity, this enhancement did not result in a higher mortality rate or the alteration of planned ALL therapy. Cancer 2003;97:2898–903. © 2003 American Cancer Society.DOI 10.1002/cncr.11390

The contribution of the factor Va C1 domain (fVa-C1) to assembly of the prothrombinase complex has not been previously investigated. The homologous fVa-C2 domain contains a binding site for phosphatidylserine (PS) that includes the indole moieties of Trp(2063)/Trp(2064) at the apex of spike-1. In order to investigate the structure and function of fVa-C1 a molecular model was constructed based on the structure of fVa-C2. The aromatic and hydrophobic side chains of Tyr (1956) /Leu (1957) in fVa-C1 are located at the predicted apex of spike-3. Exposed charged and hydrophobic residues in fVa-C1 were changed to alanine in clusters of 1-3 mutations per construct. The resultant 20 mutants were expressed in COS cells and screened for binding to immobilized PS and prothrombinase activity on phospholipid vesicles containing either 25% or 5% PS. Two mutants, (Y1956,L1957)A, and (R2023,R2027)A showed both decreased binding to immobilized PS and a selective decrease in prothrombinase activity on membranes containing 5% PS. The interaction of purified (Y1956,L1957)A with phospholipid vesicles was studied using fluorescence resonance energy transfer and prothrombinase assays. The affinity of (Y1956,L1957)A binding to 25% PS membranes was reduced 12-fold compared to rHFVa. Prothrombin activation in the presence of (Y1956,L1957)A was markedly impaired on phos-pholipid vesicles containing 10% or less PS. We conclude that solvent exposed hydrophobic and aromatic amino acids in both fVa-C1 and fVa-C2 contribute to the interaction of factor V with PS membranes.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder. Around 490 mutations in ITGA2B and ITGB3 genes were reported. We aimed to use targeted next-generation sequencing (NGS) to identify variants in patients with GT. We screened 72 individuals (including unaffected family members) using a panel of 393 genes (SHGP heme panel). Validation was done by Sanger sequencing and pathogenicity was predicted using multiple tools. In 83.5% of our cohort, 17 mutations were identified in ITGA2B and ITGB3 (including 6 that were not previously reported). In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8. The SHGP heme panel can be used as a high-throughput molecular diagnostic assay to screen for mutations and variants in GT cases and carriers. Our findings expand the molecular landscape of GT and emphasize the robustness and usefulness of this panel.

Angioimmunoblastic T cell lymphoma (AITL) is a common subtype of mature peripheral T cell lymphoma (PTCL). As per the 2016 World Health Organization classification, AITL is now considered as a subtype of nodal T cell lymphoma with follicular helper T cells. The diagnosis is challenging and requires a constellation of clinical, laboratory and histopathological findings. Significant progress in the molecular pathophysiology of AITL has been achieved in the past two decades. Characteristic genomic features have been recognized that could provide a potential platform for better diagnosis and future prognostic models. Frontline therapy for AITL was mainly depending on chemotherapy and the management of relapsed or refractory AITL is still unsatisfactory with a very poor prognosis. Upfront transplantation offers better survival. Novel agents have been introduced recently with promising outcomes. Several clinical trials of combinations using novel agents are underway. Herein, we briefly review recent advances in AITL diagnosis and the evolving treatment landscape.

Background Bleeding disorders vary in prevalence. While some are rare, some can be common in both sexes. Most bleeding disorders manifest as chronic bleeding tendencies or as an increase in bleeding during surgical procedures or trauma. The consequences of bleeding can be as simple as iron deficiency or catastrophic, resulting in severe morbidity and mortality. Bleeding disorders typically affect both sexes except hemophilia A and B, which mainly affects males. Method We conducted a questionnaire-based survey among adolescents and young adults (1901 [49%] boys, 1980 [51%] girls) in Riyadh city regarding bleeding symptoms. Of these, 1849 (47.6%) responded “Yes/Positive” for at least one question about the bleeding symptoms. Results The most common bleeding symptom was epistaxis (19.7% of the sample population) detected in Phase I of the study. A tandem survey was conducted among 525 adolescents who had responded “Yes/Positive” to any one of the questions inquiring about bleeding symptoms. Conclusion In this study, we report for the first time the prevalence of bleeding symptoms in a representative sample of Saudi adolescents and young adults.

Different types of mutations have been reported in patients with hemophilia A. Although about half of all severe factor VIII deficiencies are caused by gene rearrangements (inversions) involving intron 22 in F8, other mutations such as point mutation, large deletions and insertions had been reported. We report the result of the first molecular testing for or F8 mutations from Saudi Arabia. A cohort of 22 men with hemophilia A was studied for F8 mutations. All patients were tested for factor VIII coagulant activity and inhibitors. Peripheral blood samples were used for DNA extraction followed by PCR detection of intron 22 inversion and all samples tested negative were screened for other F8 mutations. The patient's age ranged between 4 and 37 years. All patients except two siblings had severe hemophilia A. Only two patients out of 22 developed inhibitors with no obvious relation to the genotype. F8 Intron 22 inversion was detected in 10 patients (50%) of severe cases. Additionally, five point mutations and one deletion/insertion involving different exons were detected. All identified mutations were associated with severe phenotype except for one, which was associated with mild phenotype of hemophilia. This is the first report of molecular genotype of hemophilia A in the Saudi population and one of the few for Arab population. We had confirmed the incidence of Inversion 22 in severe hemophilia. We are reporting two novel mutations in F8, which can be used for carrier detection and prenatal genetic diagnosis (PGD).

These results suggest that the MEA is sensitive for the detection of Glanzmann thrombasthenia. Furthermore, MEA may also be able to differentiate between the subtypes of Glanzmann thrombasthenia.