4 research outputs found
Clinical Phenotype of Bernard Soulier Syndrome Case Resulting from Compound Heterozygous Inheritance
Background: Bernard Soulier Syndrome (BSS) is a rare, autosomal recessive inheritance disorder of platelet function. Estimated to affect one per one million, there are currently only 200 cases reported worldwide presenting more commonly in families with parental consanguinity.
This syndrome occurs when there is a genetic defect in the subunits (GPIb-alpha, GPIB-beta, and GP9) that form the GPIb-IX-V complex. The result is inadequate binding to von Willebrand factor. The clotting cascade is, therefore, unable to begin, causing symptoms of excessive and prolonged bleeding.
Objectives: We report a case with multiple episodes of exaggerated bleeding and easy bruising.
Methods: We analyzed complete blood count, coagulation studies, platelet aggregation assays, platelet glycoprotein expression by flow cytometry, as well as screened both patient and parents for relevant genes responsible for BSS.
Results: 14-month-old Caucasian male born at 38w3d gestational age, non-consanguineous parents with multiple episodes of exaggerated bleeding and easy bruising from minor injuries. His symptoms started early in life with excessive bleeding after circumcision. No history of intramuscular, joint, or intracranial bleeding.
Complete blood counts showed macrothrombocytopenia (98 X109 /L MPV 12.3 fl) no leukocyte inclusion bodies on peripheral smear. Coagulation tests (prothrombin time, activated partial thromboplastin time, vWF antigen, and vW-Ristocetin cofactor activity, platelet function assay) were normal. Platelet glycoprotein expression by flow cytometry revealed significantly reduced binding of monoclonal antibodies to platelet GPIb and normal GPIIb/IIIa. Comprehensive platelet disorder panel revealed two clinically significant variants missense mutations in the GP9 gene (P.Cys135 Tyr and P.Asn61Ser) These variants were on opposite alleles and results were consistent with the diagnosis of Bernard Soulier syndrome (BSS). The mother reported heavy menstrual cycles, the father had no significant bleeding symptoms, and both parents had normal platelet counts. Target genetic testing identified these two distinct missense mutations from both Mother and Father of the child.
Conclusion: The two rare variants occurring on the gene for GPIX (GP9) increase the number of known genetic defects associated with the manifestation of Bernard Soulier Syndrome
Peroxiredoxin II (PRDX2) Is a Novel Candidate Gene for Congenital Dyserythropoietic Anemia
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MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type
Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the BCL6 transcriptional complex was performed using electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of BCL6, CD10, and ERK phosphorylation. Analysis of BCL6 transcription factors in nuclear extracts of MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2 alpha and BCL6 proteins in the formation of the BCL6 gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in tissue microarray, as indicated via immunohistochemistry (Visco-Young algorithm). Our findings indicate that MEF2B is an essential component of the BCL6 gene transcriptional complex for the regulation of DLBCL growth via the promotion of BCL6 expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with BCL6 and CD10 expression, and was preferentially expressed in the GBC-DLBCL group