ABSTRACT
BACKGROUND: Neonatal purpura fulminans due to congenital protein C deficiency is a rare disorder. CASE CHARACTERISTICS: A four-day-old neonate presented with multiple necrotic skin lesions with abnormal coagulation profile. INTERVENTION AND OUTCOME: Skin lesions responded to repeated plasma transfusions but the neonate developed bilateral retinal detachment. A novel homozygous PROC gene mutation was noted in the neonate. MESSAGE: Molecular diagnosis and prenatal counseling in neonatal purpura fulminans are vital considering the poor outcome.
Subject(s)
Protein C Deficiency , Protein C/genetics , Purpura Fulminans , Humans , Infant, Newborn , Male , Mutation/genetics , Necrosis/pathology , Thigh/pathologySubject(s)
Factor XI Deficiency/epidemiology , Factor XI Deficiency/genetics , Factor XI/genetics , Adolescent , Adult , Aged , Amino Acid Sequence , Child , Child, Preschool , Conserved Sequence , Factor XI/analysis , Factor XI/chemistry , Factor XI Deficiency/blood , Factor XI Deficiency/complications , Female , Hemorrhage/blood , Hemorrhage/etiology , Hemorrhage/genetics , Humans , India/epidemiology , Male , Middle Aged , Molecular Epidemiology , Mutation , Mutation, Missense , Young AdultABSTRACT
Chromosomal abnormalities are important in the diagnosis and prognosis of patients with acute myeloid leukemia (AML). The purpose of this study was to identify DNA copy number variations in karyotypically normal AML patients and their correlation with immunophenotypes. Conventional comparative genomic hybridization (CGH) and immunophenotyping were performed in 46 untreated AML patients aged 7-68 years. Among the 86 Indian patients who had AML, 40 (46.5%) showed an abnormal karyotype and 46 (53.4%) showed no chromosome aberrations. The karyotypically abnormal AML patients were excluded from the study. Out of the 46 patients without chromosomal aberrations, 24 (52.2%) showed DNA copy number variations including losses and gains. The DNA copy number variations involved chromosomes 1, 3, 6, 12, 15, 16, 17 (gains) and 1, 4, 2, 3, 5, 7, 8, 9, 10, 11, 13, 15, 18, 20, 21 (losses). The aberrant immunophenotype was noticed in 13 of these 24 (54%) cases. The hidden chromosome rearrangements in karyotypically normal AML, which could not be detected by conventional cytogenetics and fluorescence in situ hybridization, were detected by CGH. These genetic changes have an important role in the prognosis of the disease. The DNA copy number changes might also be involved in the aberrant immunophenotypes in our study.
Subject(s)
Comparative Genomic Hybridization/methods , DNA Copy Number Variations/genetics , Immunophenotyping/methods , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Adolescent , Adult , Aged , Child , Chromosomes, Human/genetics , Cytogenetics , Female , Humans , In Situ Hybridization, Fluorescence , India , Karyotyping , Male , Middle Aged , Young AdultABSTRACT
The myelodysplastic syndromes (MDS) are clonal disorders of haematopoietic stem cells characterized by ineffective haematopoiesis leading to blood cytopenias and by high incidence of progression to acute myeloid leukaemia (AML). These disorders generally arise de novo, but may also occur years after exposure to mutagenic chemotherapy. Clonal cytogenetic abnormalities are detected in about 30-50% de novo cases, whereas more than 80% of therapy-related forms harbour such markers. Although in the Western countries, MDS cases are mainly reported in the elderly population and rarely in the paediatric age group; this disease is increasingly seen in young adults in India. Cytogenetic study plays an important role in the diagnosis and is useful for prediction of individual prognosis using the international prognostic scoring system. Specific chromosomal abnormalities, such as -5/5q-, -7/7q-, and complex abnormalities, play an important role in the development of new therapeutic options and clinical management of MDS. In this review, we summarize the cytogenetic abnormalities in MDS from various parts of the world.
Subject(s)
Chromosome Aberrations , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Chromosome Deletion , Chromosomes, Human, Pair 5/genetics , Chromosomes, Human, Pair 7/genetics , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Myelodysplastic Syndromes/classification , Prognosis , Translocation, GeneticABSTRACT
INTRODUCTION: Myelodysplastic syndromes (MDSs) are clonal stem cell disorders characterized by cytopenias, dysplasia in one or more cell lineages and ineffective hematopoiesis and are associated with significant morbidity and mortality due to bone marrow failure or evolution to acute myeloid leukemia. Clonal chromosomal abnormalities are detected in 40-60% of patients. Multiple recurrent chromosomal aberrations have been identified by cytogenetics including fluorescence in situ hybridization (FISH) which is now widely recognized as one of the most important diagnostic and prognostic markers in MDS. METHODS: Conventional cytogenetics by GTG-banding, FISH, comparative genomic hybridization (CGH) was done on 40 primary MDS subjects. RESULTS: Among 40 subjects, 10 (25%) were abnormal and 30 (75%) showed apparently normal karyotypes with GTG banding and FISH. The various aberrations observed were del 5q-, del 7q-, 20q-, +8. DNA copy number changes including losses (30%) and gains (20%) were detected by CGH in 11 (36.6%) out of 30 karyotypically normal MDS. However chromosome 7 (37%) and 1 (25%) is frequently involved in current study population. CONCLUSIONS: This study confirms that the apart from non-random chromosome aberrations, other chromosome regions also involved in the MDS development. The occupational, environmental and geographical variations might be influencing the disease. Furthermore cytogenetic studies are warranted in larger groups of MDS cases to identify newly acquired chromosome aberrations that may aid in cloning new genes involved in the neoplastic process, ultimately helping in the development of targeted therapeutic drugs.
