ABSTRACT
ABSTRACT Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.
El síndrome mielodisplásico con deleción del cromosoma 5q (síndrome 5q) tiene un pronóstico favorable y riesgo bajo de transformación a leucemia aguda en pacientes que son tratados con lenalidomida (tratamiento estándar). El uso Azactidina tiene respuestas completas incluso como segunda línea de tratamiento en pacientes con evolución clonal. Presentamos una mujer de 71 años, sin exposición a mielotóxicos que debutó con un síndrome anémico. Se realizó biopsia de medula ósea que mostró celularidad del 50% y en el análisis citogenético se detectó una deleción del cromosoma 5 en 22% de las metafases analizadas, lo que llevó al diagnóstico de Síndrome 5q- de riesgo bajo de acuerdo con el puntaje IPSS-R (Revised International Prognostic Scoring System). Ya que no se pudo costear lenalidomida, se trató con talidomida (100 mg/día). Permaneció tres años sin requerir soporte transfusional. Posteriormente, presentó pancitopenia y en el nuevo aspirado de médula ósea se observó displasia de la serie roja y megacariocitos, con cariotipo complejo y peor pronóstico (IPSS-R 5 puntos). Se trató con 12 ciclos de azacitidina con lo que logró respuesta completa. Recayó 12 meses después y continuó manejo de soporte por un año. Finalmente falleció debido a un accidente vascular cerebral.
Subject(s)
Aged , Female , Humans , Thalidomide , Myelodysplastic Syndromes , Chromosome Deletion , Angiogenesis Inhibitors , Anemia, Macrocytic , Thalidomide/therapeutic use , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/drug therapy , Chromosomes, Human, Pair 5/genetics , Treatment Outcome , Angiogenesis Inhibitors/therapeutic use , Lenalidomide , Anemia, Macrocytic/genetics , Anemia, Macrocytic/drug therapyABSTRACT
Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected novel nine candidate loci for CGD2. In simulation analysis, the only 3q26.3 region including neuroligin 1 gene (NLGN1) was supported by empirical statistic significance. To investigate the effect of genetic heterogeneity in linkage analysis, we classified CGD2 families into two subgroups. Although we could not find a significant evidence for correlation between the 3q26.3 region and CGD2 phenotypes, this first genome-wide analysis with CGD2 families in Korea has a very important value for offering insights in genetics of CGD2. In addition, the co-segregating loci with CGD2 including 3q26.3 would be a good target for further study to understand the pathophysiology of CGD2.
Subject(s)
Female , Humans , Male , Cell Adhesion Molecules, Neuronal/genetics , Chromosomes, Human, Pair 3/genetics , Chromosomes, Human, Pair 5/genetics , Computer Simulation , Corneal Dystrophies, Hereditary/genetics , Genetic Linkage , Genetic Loci , Genome-Wide Association Study , Genotype , Models, Genetic , Polymorphism, Single Nucleotide , Transforming Growth Factor beta1/geneticsABSTRACT
Detection of genetic alterations could provide a tool as an adjuvant for the diagnosis of non-small cell lung cancer (NSCLC) and to define patients at risk for early relapse. In this study, a multi-target fluorescence in situ hybridization (FISH) assay was conducted to investigate the correlation between the alterations of chromosomes, including 5p15.2, 6p11.1-q11, 7p12, and 8q24.12-q24.13 (LaVysion Test), and clinicopathological variables, and to clarify the potential of the multi-target FISH assay in 37 NSCLC. The most notable finding was the higher frequency of a gain in chromosome 5p15.2 in early-stage (I+IIa) lung cancers. The frequency of the gain was 81.3% (16/22) in stage I tumors. The frequencies of gains in 6p11.1-q11 and 8q24.12-q24.13 were 61.5% (8/13) and 84.6% (11/13) in stage IIIa cancers, as compared with lower frequencies in stage I tumors at 25.0% and 31.3%, respectively. There was also a significant difference in the histological type. Our results suggest that a gain in 6p11.1-q11 and 8q24.12-q24.13 plays an important role in tumor progression and is associated with histological differentiation. On the other hand, gene amplification in the 5p region was one of the most consistent alterations in early-stage lung cancer, and thus a series of genes in the critical 5p15.2 region might potentially associated with the development of lung cancer.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Carcinoma, Non-Small-Cell Lung/diagnosis , Chromosome Aberrations , Chromosomes, Human, Pair 5/genetics , Chromosomes, Human, Pair 6/genetics , Chromosomes, Human, Pair 8/genetics , Gene Amplification , In Situ Hybridization, Fluorescence , Lung Neoplasms/diagnosis , Neoplasm Staging , Biomarkers, Tumor/geneticsABSTRACT
Spinal muscular atrophy has been classified into four groups based on the age of onset and clinical severity of the disease. Homozygous deletion in SMN1 gene causes the disease but the clinical severity may be modified by copy number of homologous gene SMN2 as well as the extent of deletion at SMN locus. In the view of scarcity of genotype and phenotype correlation data from India, this study has been undertaken to determine that correlation in SMA patients by using the SMN and NAIP genes and two polymorphic markers C212 and C272 located in this region. Two to four alleles of the markers C212 and C272 were observed in normal individuals. However, majority of Type I patients showed only one allele from both markers whereas in Type II and III patients, 2-3 alleles were observed. The SMN2 copy number in our type III patients showed that patients carry 3-5 copies of SMN2 gene. Our results suggest that extent of deletions encompassing H4F5, SMN1, NAIP and copy number of SMN2 gene can modify the SMA phenotype, thus accounting for the different clinical subtypes of the disease.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant, Newborn , Male , Alleles , Apoptosis , Chromosomes, Human, Pair 5/genetics , Comparative Study , DNA Mutational Analysis , Cyclic AMP Response Element-Binding Protein/genetics , Enzyme Inhibitors/metabolism , Gene Deletion , Genetic Markers , Genotype , Homozygote , India , Muscular Atrophy, Spinal/genetics , Nerve Tissue Proteins/genetics , Phenotype , RNA-Binding Proteins/genetics , Genetic VariationABSTRACT
In order to investigate whether Arg110Gln polymorphism in the coding region of the IL-13 gene is associated with asthma and total plasma IgE level in Han nationality in Hubei Chinese population, the allele frequency of 4257(g/a) site and Arg110Gln genotype of IL-13 was detected by using restriction fragment length polymorphism in Han nationality in Hubei Chinese population including 43 asthmatic children, 45 asthmatic adults, 31 control children and 46 control adults. Total plasma IgE was measured by Chemiluminescence assay. The results showed that the frequency of allele A at 4257 bp of IL-13 in children and adults was 0.39 and 0.32, respectively. The GlnGln form of Arg110Gln polymorphism of IL-13 gene was associated with susceptibility of asthma and elevated total plasma IgE in children (P=0.030 and 0.0009, respectively), but not with them in adults (P=0.219 and 0.174, respectively). Our results suggest that the Arg110Gln polymorphism of IL-13 gene is associated with susceptibility of asthma and elevated total plasma IgE in Chinese children of Han nationality in Hubei, but not with them in adults.
Subject(s)
Asthma/genetics , China/ethnology , Chromosomes, Human, Pair 5/genetics , Gene Frequency , Genetic Predisposition to Disease/genetics , Immunoglobulin E/blood , Interleukin-13/genetics , Polymorphism, Genetic/geneticsABSTRACT
This study was carried out with 33 spinal muscular atrophy [SMA] patients. DNA molecular studies of the SMA gene on the long arm of chromosome 5 [5q11.2q13.3] revealed homozygous deletion of exon 7 in 55% of cases, 36% of whom also had a homozygous delition of exon 8. The adult patients were heterozygous for an abnormal size exon 8. The remaining patients had either compound heterozygote deletion of exons 7 and 8 or were normal for both. There may therefore be 5q-unlinked SMA or SMA due to other mutations. Detection of deletions of SMA exons 7 and 8 is a powerful diagnostic test in patients with SMA, but other mutations among Egyptians must also be sought
Subject(s)
Adult , Child , Female , Humans , Infant , Male , Age of Onset , Case-Control Studies , Chromosomes, Human, Pair 5/genetics , DNA Mutational Analysis/methods , Disease Progression , Gene Deletion , Heterozygote , Homozygote , PhenotypeABSTRACT
The 5q- syndrome is a rare clinical and biological entity, included in the myelodysplastic syndromes, although the original FAB classification did not mention it. We report three observations of this syndrome. The diagnosis was suspected on the hemogram and myelogram data, and was confirmed by the karyotype. The three patients were women, aged 44, 63 and 69 years respectively. Anemic syndrome was the main reason of consultation. Anemia was macrocytic, aregenerative, Hb level was 8g/dl in 2 patients and 3.7 g/dl in the third one. The leukocyte number was normal in the three patients. Platelet number was increased in 2 patients, and normal in one. The myeloblast percentage did not exceed 4% in all cases, while erythroblasts were increased in one case. A dysmegakaryocytopoiesis, with numerous micromegakaryocytes and hypo- or bilobulated megakaryocytes was found in all cases. The karyotype revealed a deletion of the long arm of chromosome 5, which was isolated in 2 patients, with del 5 [q[13], q[31]] and del 5 [q[13], q[33]] respectively, and associated to a deletion of chromosome 13 in the third patient exhibiting del 5 [q[12], q[31]] + del 13 [q[12],q[14]]. One patient has been treated by erythropoietin and G-CSF and the two others by folates;androgens and bloodtransfusions. All three patients are still alive with a mean follow-up duration of 40 months
Subject(s)
Humans , Female , Chromosome Deletion , Chromosome Aberrations , Chromosomes, Human, Pair 5/geneticsABSTRACT
Se describe el caso de una mujer de raza blanca, de 30 años de edad, con anemia crónica de 3 años de evolución, refractaria a tratamiento médico y a esplenectomía. Los estudios citogenéticos demostraron una anomalía única, la delección parcial del brazo largo del cromosoma No. 5, defecto denominado "Síndrome del 5q-" descrito en aproximadamente 15 pacientes en la literatura mundial. Este síndrome aparentemente adquirido se caracteriza por anemia refractaria, moderada leucopenia, trombosistosis e hipolobulación de los megacariocitos. La anemia es resistente a los tratamientos conocidos y no evoluciona a leucemia aguda. La mayor parte de los pacientes fallecen por las complicaciones de la hemosiderosis producida por la gran cantidad de transfusiones que requieren para mantener una hemoglobina adecuada. La terapia quelante de hierro con desferroxamina, utilizando minibombas de infusión continua, es, hasta el momento, la única forma de prevenir la muerte por falla cardíaca en los pacientes dependientes de transfusiones. Este es el primer caso del "Síndrome del 5q-" informado en la literatura médica colombiana