ABSTRACT
INTRODUCTION: Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain cases genotype-phenotype correlations are important for predicting the clinical course of the disease and to allow tailor-made follow-up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next-generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost. AIM: The aim of this study was to design and to analyse the applicability of a 23-gene NGS panel in the molecular diagnosis of patients with IBCDs. METHODS: A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology. RESULTS: In all patients, our NGS approach detected causative mutations. Twenty-one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant. CONCLUSION: Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs.
Subject(s)
Blood Coagulation Disorders, Inherited/genetics , Genetic Testing/methods , Adolescent , Adult , Blood Coagulation Disorders, Inherited/pathology , Child , Child, Preschool , DNA/chemistry , DNA/isolation & purification , DNA/metabolism , Female , Frameshift Mutation , Gene Deletion , Genetic Association Studies , Genotype , High-Throughput Nucleotide Sequencing , Humans , Infant , Male , Middle Aged , Mutation, Missense , Sequence Analysis, DNA , Young AdultABSTRACT
Although multiparameter flow cytometry (MFC) has demonstrated clinical relevance in monoclonal gammopathy of undetermined significance (MGUS)/myeloma, immunophenotypic studies on the full spectrum of Waldenström's Macroglobulinemia (WM) remain scanty. Herein, a comprehensive MFC analysis on bone marrow samples from 244 newly diagnosed patients with an immunoglobulin M (IgM) monoclonal protein was performed, including 67 IgM-MGUS, 77 smoldering and 100 symptomatic WM. Our results show a progressive increase on the number and light-chain-isotype-positive B-cells from IgM-MGUS to smoldering and symptomatic WM (P<.001), with only 1% of IgM-MGUS patients showing >10% B cells or 100% light-chain-isotype-positive B-cells (P<.001). Complete light-chain restriction of the B-cell compartment was an independent prognostic factor for time-to progression in smoldering WM (median 26 months; HR: 19.8, P=0.001) and overall survival in symptomatic WM (median 44 months; HR: 2.6, P=0.004). The progressive accumulation of light-chain-isotype-positive B-cells accompanied the emergence of a characteristic Waldenstrom's phenotype (CD22(+dim) / CD25+ /CD27+ / IgM+) that differed from other B-NHL by negative expression of CD5, CD10, CD11c or CD103. In contrast to myeloma, light-chain-isotype-positive plasma cells in IgM monoclonal gammopathies show otherwise normal antigenic expression. Our results highlight the potential value of MFC immunophenotyping for the characterization of the Waldenström's clone, as well as for the differential diagnosis, risk of progression and survival in WM.
Subject(s)
Flow Cytometry/methods , Immunoglobulin M/blood , Monoclonal Gammopathy of Undetermined Significance/blood , Waldenstrom Macroglobulinemia/blood , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Risk AssessmentABSTRACT
Presentación del programa institucional que conecta centros de Atención Primaría con hospitales a través de una intranet con una aplicación web. Base de datos informix y programación asp integrada con los sistemas de identificación y gestión de AP (AU)
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Subject(s)
Primary Health Care , Health Services Accessibility , Telemedicine/trends , Telemedicine , Health Information Systems , Internet , Epidemiological Monitoring/trends , Health Services , Spain/epidemiologyABSTRACT
Castleman's disease (CD) is a enigmatic lymphoid disease of unknown etiology which rarely manifest itself as an isolated pelvic mass. We report a case of pelvic Castleman's disease masquerading as a uterine myoma. The patient presented symptoms related to compression of adjacent structures, splenomegaly and abdominal lymphadenopathy, the laboratory data revealed positive Epstein-Barr virus serology, elevated beta 2-microglobulin level and presence of antinuclear antibodies. The intraabdominal involvement, histological patterns and clinical forms of this condition are reviewed. Likewise etiopathogenic, radiologic and therapeutic aspects related with this entity are discussed. We suggest that pelvic Castleman's disease should be included in the differential diagnosis of females presenting a pelvic mass containing calcifications.
Subject(s)
Calcinosis/diagnosis , Castleman Disease/diagnosis , Leiomyoma/diagnosis , Pelvis , Uterine Neoplasms/diagnosis , Antibodies, Antinuclear/blood , Antibodies, Viral/blood , Calcinosis/immunology , Calcinosis/pathology , Calcinosis/virology , Castleman Disease/immunology , Castleman Disease/pathology , Castleman Disease/virology , Female , Herpesviridae Infections/diagnosis , Herpesviridae Infections/immunology , Herpesviridae Infections/pathology , Herpesviridae Infections/virology , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/isolation & purification , Humans , Middle Aged , beta 2-Microglobulin/analysisABSTRACT
We report a case of rheumatoid arthritis with anterior and vertical atlantoaxial subluxation. Our patient developed severe spastic quadriparesis and pyramidal tract signs. Cephalic computerized tomogram scan showed evidence of evolutive communicating hydrocephalus and the odontoid peg protruding in the posterior fossa. The patient recovered after cerebral spinal fluid ventricle-peritoneal shunting and occipitocervical arthrodesis. No other neurologic complications occurred during a 6-year followup.
