RESUMEN
ICF syndrome is a rare autosomal recessive disease characterized by variable immunodeficiency, centromeric instability, and facial abnormalities. Mutations in the catalytic domain of DNMT3B, a gene encoding a de novo DNA methyltransferase, have been recognized in a subset of patients. ICF syndrome is a genetic disease directly related to a genomic methylation defect that mainly affects classical satellites 2 and 3, both components of constitutive heterochromatin. The variable incidence of DNMT3B mutations and the differential methylation defect of alpha satellites allow the identification of two types of patients, both showing an undermethylation of classical satellite DNA. This classification illustrates the specificity of the methylation process and raises questions about the genetic heterogeneity of the ICF syndrome.
Asunto(s)
Anomalías Craneofaciales/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN , Síndromes de Inmunodeficiencia/genética , Mutación , Centrómero , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Empalme del ARN , Análisis de Secuencia de ADN , Síndrome , ADN Metiltransferasa 3BAsunto(s)
Síndrome de Denys-Drash/genética , Disgenesia Gonadal 46 XY/complicaciones , Disgenesia Gonadal 46 XY/genética , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/genética , Adulto , Cartilla de ADN/genética , Femenino , Humanos , Inteínas/genética , Mutación Puntual/genética , Turquía , Proteínas WT1/genéticaRESUMEN
We report on a girl aged 16 months with localized gigantism of the lower limb and widespread subcutaneous lipomas. This is the first case of macrodystrophia lipomatosa with lipomatous involvement in areas other than the involved limb.
Asunto(s)
Deformidades Congénitas del Pie/genética , Pierna/fisiopatología , Lipomatosis/genética , Abdomen/patología , Femenino , Deformidades Congénitas del Pie/fisiopatología , Humanos , Lactante , Pierna/anomalías , Lipomatosis/fisiopatología , Imagen por Resonancia Magnética , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
The association of mullerien duct with gonadal dysgenesis is extremely rare. We report such a case in a 19 year-old white woman with a 46,X,del(X)(pter-->q22:) karyotype.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos X , Disgenesia Gonadal/genética , Adulto , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Ovario/anomalías , Síndrome , Útero/anomalíasRESUMEN
Butterfly vertebra is a rare congenital anomaly associated with syndromes such as Pfeiffer, Jarcho-Levin, Crousen, Alagille. In the literature, only a few cases of butterfly vertebra have been reported as incidental finding. We described a 37-year-old male who had an L3 butterfly vertebra associated with an L4-L5 disc protrusion. Awareness of this anomaly is important for making correct diagnosis. Although this uncommon anomaly is considered to be usually asymptomatic, we suggest that it might increase the incidence of disc herniation, because the condition may alter the spinal biomechanics.
Asunto(s)
Desplazamiento del Disco Intervertebral/diagnóstico , Vértebras Lumbares/anomalías , Adulto , Humanos , Vértebras Lumbares/patología , Imagen por Resonancia Magnética , MasculinoAsunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 21/genética , Síndrome de Down/genética , Bandeo Cromosómico , Inversión Cromosómica , Síndrome de Down/patología , Salud de la Familia , Femenino , Duplicación de Gen , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Linaje , Recombinación GenéticaRESUMEN
Several rare autosomal folate sensitive fragile sites were reported in individuals with mental retardation, neurological abnormalities, and multiple congenital malformations. Only three of them: fra(11)(q22.3), fra(X)(q27.3) and fra(X)(q28), are known to be associated with mental retardation and phenotypic abnormalities. A possible association of the other rare fragile sites with idiopathic mental retardation is still being discussed. Here, a girl who has a fragile site at 2q11 with minor congenital anomalies and mental retardation is presented. This case has recalled the question of idiopathic mental retardation that might be the clinical expression of rare FSFS. Fragility was observed at 2q11 with a frequency of 3% in her cells along with a partial endoreduplication at 2 q11-->qter.
Asunto(s)
Fragilidad Cromosómica/genética , Cromosomas Humanos Par 2/genética , Discapacidad Intelectual/genética , Niño , Sitios Frágiles del Cromosoma , Femenino , Humanos , FenotipoRESUMEN
The two constitutive heterochromatin (alpha- and beta-satellite DNA) probes of human acrocentric chromosomes were assayed separately to label the nucleoli in the phytohemagglutinin (PHA)-stimulated human lymphocytes. Fluorescent in situ hybridisation (FISH) results have shown that: a) whole (100%) signal-nucleoli overlapping was obtained with both heterochromatin probes in maximally activated nuclei (MANs); b) partial overlapping was observed in non-activated or slightly activated nuclei; c) random signal-nucleolus overlapping (background level) was found to be approximately 6% by the NOR-irrelevant euchromatic probe (D5S23); d) Yq-nucleolus association in the MANs was found to be approximately 97% without the subtraction of the background level. We concluded that: a) acrocentric alpha- or beta-satellite DNA probes may be used as nucleolar markers only in the MANs and not in slightly activated or non-activated nuclei; b) the distances between rDNA loci and alpha-/beta-satellite DNA on human acrocentrics are short enough to permit their observation on the same nucleolus.
Asunto(s)
Nucléolo Celular/genética , Cromosomas Humanos/genética , ADN Satélite/análisis , Heterocromatina/genética , Linfocitos/efectos de los fármacos , Fitohemaglutininas/farmacología , Cromosomas Humanos/metabolismo , Sondas de ADN/química , Eucromatina/genética , Humanos , Hibridación Fluorescente in Situ , Activación de Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Región Organizadora del Nucléolo , FotomicrografíaRESUMEN
OBJECTIVE: Behçet's disease (BD) is a multisystemic disease of unknown etiology, characterized by aphthous ulcerations and uveitis, that is common in the Turkish population. Venous involvement is observed in 25% of the cases. While superficial thrombophlebitis is the most common finding, deep venous thrombosis (DVT) follows it. Hyperactivity in the coagulation pathway, hypoactive anticoagulation mechanisms, or faulty fibrinolysis generate a tendency for thrombogenesis. Mutations of the genes involved in these pathways may cause predisposition to thrombosis. METHODS: Possible roles of methylenetetrahydrofolate reductase (MTHFR) gene C677T, factor V (FV) gene G1691A (Leiden), and prothrombin gene G20210A polymorphisms in venous thrombogenesis were evaluated in patients with BD; 100 healthy people, 30 BD patients without DVT, 30 BD patients with DVT, and 30 patients with idiopathic DVT were studied with the restriction fragment length polymorphism method for these 3 polymorphisms. The frequencies of these mutations for each group, separately and in combinations, are described. RESULTS: Among the 3 mutations, FV Leiden mutation was found to be a risk factor for DVT. An association between FV Leiden mutation and BD was likely, but FV Leiden mutation did not increase the risk for deep venous thrombogenesis in BD patients. MTHFR gene C677T mutation does not increase risk of DVT in BD either alone or combined with FV Leiden mutation. CONCLUSION: Although a thrombotic tendency is one of the major characteristics of BD, we found no association between these 3 thrombogenetic mutations and BD patients with thromboses.
Asunto(s)
Síndrome de Behçet/genética , Factor V/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Protrombina/genética , Trombosis de la Vena/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Síndrome de Behçet/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Mutación Puntual , Factores de Riesgo , Trombosis de la Vena/etiologíaRESUMEN
BACKGROUND: Observations with intravascular ultrasound demonstrated that neointimal hyperplasia is the predominant factor responsible for in-stent restenosis. Experimental data suggest that angiotensin I converting enzyme (ACE) plays a role in the thickening of neointima after balloon denudation. Insertion/deletion (I/D) polymorphism of the ACE gene is significantly associated with plasma level of ACE and subjects with D/D genotype have significantly higher plasma levels of ACE than normal. OBJECTIVE: To investigate whether this polymorphism influences the risk of restenosis after coronary stenting. METHODS: We genotyped 158 patients who had undergone single-vessel coronary stenting for the ACE I/D polymorphism. RESULTS: Of the 158 patients, 56 (35%) had the D/D genotype, 71 (45%) had the I/D genotype and 31 (20%) had the I/I genotype. Prevalences of genotypes were compatible with Hardy-Weinberg equilibrium and distributions of ACE genotype among patients and 132 healthy controls from the same geographic area did not differ. At follow-up (after a median duration of 5.4 months), overall rates of angiographic restenosis and of revascularization of target lesion (RTL) were 32.3 and 22.8%, respectively. Of 51 patients with angiographic restenosis, 31 (60.8%) had focal and 20 (39.2%) had diffuse patterns of restenosis. Diffuse in-stent restenosis was significantly more prevalent among patients with D/D genotype (P = 0.016). Multiple stepwise logistic regression analysis identified ACE I/D polymorphism as the independent predictor of angiographic restenosis and RTL. Relative risk of angiographic restenosis was 6.29 [95% confidence interval (CI), 1.80-22.05, P = 0.0004] for D/D genotype and 3.88 (95% CI 1.11-13.12, P = 0.029) for I/D genotype, whereas relative risk of RTL was 7.44 (95% CI 1.60-34.58, P = 0.01) for D/D genotype and 3.88 (95% CI 0.083-18.15, P = 0.085) for I/D genotype. CONCLUSIONS: The ACE I/D polymorphism is significantly associated with risk of angiographic and clinical restenosis after coronary stenting. Angiographic pattern of restenosis is also significantly associated with I/D polymorphism, diffuse type being more prevalent among subjects with D/D genotype.
Asunto(s)
Enfermedad Coronaria/genética , Elementos Transponibles de ADN , Eliminación de Gen , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Stents , Angiografía Coronaria , Enfermedad Coronaria/terapia , Femenino , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/sangre , RecurrenciaRESUMEN
In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.
Asunto(s)
Antineoplásicos/toxicidad , Ciclofosfamida/orina , Linfocitos/citología , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Mucosa Bucal/citología , Enfermeras y Enfermeros/estadística & datos numéricos , Adulto , Factores de Edad , Femenino , Humanos , Linfocitos/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/genética , Mucosa Bucal/efectos de los fármacos , Exposición Profesional/estadística & datos numéricos , Factores Sexuales , Fumar , TurquíaRESUMEN
The TP53 gene has been extensively studied in patients with chronic myeloid leukemia (CML), both in chronic phase and in blast crisis. Mutations in the gene were found in up to 30% of the patients, especially among those in blast crisis. We report the results of an analysis of 29 blood samples from CML patients: 8 samples from chronic phase patients, 8 from patients in the accelerated phase, and 13 from patients in blast crisis. By using genomic DNA, we sequenced PCR products of the coding exons and most introns of the TP53 gene, finding genetic changes in 30% of the blast crisis samples and 12% in chronic phase. All mutations were found in introns and were previously unreported. Immunocytochemical studies revealed accumulation of TP53 in blood cells of samples both from chronic phase and blast crisis patients. Since these samples had no TP53 mutations, we believe that wild type TP53 accumulates in blood cells of CML patients. Our results, therefore, indicate that molecular changes in coding regions of the TP53 gene are rare. The significance of the abundance of intronic changes should be investigated further. Accumulation of wild type TP53 in CML cells may indicate an additional mechanism involving this gene in the pathogenesis of this disease.
Asunto(s)
Genes p53 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucocitos/metabolismo , Adulto , Anciano , ADN de Neoplasias/sangre , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Intrones , Leucocitos/química , Masculino , Persona de Mediana Edad , Mutación PuntualRESUMEN
The parental origin and mechanism of formation of polysomy X were studied in two polysomic cases, using four X-linked restriction fragment length polymorphisms, three (CA)n dinucleotide repeat sequences and one variable number tandem repeat (VNTR) locus as genetic markers. A nonradioactive technique based on the hybridization of the polymerase chain reaction (PCR) product was developed for the analysis of dinucleotide repeats. Segregation analysis using different nonradioactive approaches based on the PCR, revealed that all four X chromosomes were of maternal origin. These data provide additional evidence of an identical mechanism of successive nondisjunctions in maternal meiosis I and II.
Asunto(s)
Aneuploidia , Aberraciones Cromosómicas/genética , Cromosoma X , Adulto , Preescolar , Trastornos de los Cromosomas , Discapacidades del Desarrollo/genética , Repeticiones de Dinucleótido , Enfermedades en Gemelos , Cara/anomalías , Femenino , Marcadores Genéticos , Heterocigoto , Humanos , Discapacidad Intelectual/genética , Cariotipificación , Masculino , Polimorfismo de Longitud del Fragmento de Restricción , Embarazo , Secuencias Repetitivas de Ácidos Nucleicos , Gemelos DicigóticosRESUMEN
We report three new mutations in the gene for aldolase B that are associated with hereditary fructose intolerance (HFI). Two nonsense mutations create opal termination codons: R3op (C-->T, Arg3-->ter, exon 2) was found in homozygous form in four affected members of a large consanguineous Turkish pedigree and R59op (C-->T, Arg59-->ter, exon 3) was found on one allele in a woman of Austrian origin known to harbour one copy of the east European mutation, N334K (Asn334-->Lys). The third mutation occurred in a French HFI patient known to be heterozygous for the widespread mutation, A174D (Ala174-->Asp): a single mutation, G-->A, in the consensus acceptor site 3' of intron 6 was found on the remaining allele. These mutations are predicted to abrogate synthesis of functional protein and thus represent null alleles of aldolase B. The mutant alleles can be readily detected in the amplification refractory mutation system (ARMS) or (for R59op and 3' intron 6) by digestion of amplified genomic fragments with DdeI or A1wNI, respectively, to facilitate direct diagnosis of HFI by molecular analysis of aldolase B genes.
Asunto(s)
Alelos , Intolerancia a la Fructosa/genética , Fructosa-Bifosfato Aldolasa/deficiencia , Mutación Puntual , Secuencia de Bases , Consanguinidad , Análisis Mutacional de ADN , Cartilla de ADN , Femenino , Fructosa-Bifosfato Aldolasa/genética , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la Polimerasa , TurquíaRESUMEN
Cytogenetic analysis was performed on a four-year-old girl with obesity, mental retardation, recurrent febrile convulsions and a provisional diagnosis of Prader Willi syndrome. High-resolution banding was done to observe the subchromosomal deletion. An interstitial deletion (q11-->q13) on one of the 15th chromosomes was observed in all metaphases.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 15 , Síndrome de Prader-Willi/genética , Preescolar , Femenino , Humanos , Cariotipificación , Linfocitos/patología , Metafase , Síndrome de Prader-Willi/diagnósticoRESUMEN
A 6-year-old Turkish boy with bilateral orbito-ocular granulocytic sarcoma and AML is described. Cytogenetic studies on peripheral blood disclosed an abnormal hyperdiploid population with a double Ph chromosome. Despite intensive chemotherapy, he achieved only partial remission. Repeated cytogenetic studies on bone marrow during relapse revealed the persistence of double Ph chromosome. The aggressive course and the short survival time of this patient, despite adequate chemo-radiotherapy, may be explained by the presence of the double Ph chromosome.
Asunto(s)
Neoplasias del Ojo/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Neoplasias Primarias Múltiples/genética , Neoplasias Orbitales/genética , Cromosoma Filadelfia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Terapia Combinada , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/radioterapia , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/radioterapia , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/radioterapia , Masculino , Metotrexato/administración & dosificación , Familia de Multigenes , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/radioterapia , Neoplasias Orbitales/tratamiento farmacológico , Neoplasias Orbitales/radioterapia , Tioguanina/administración & dosificaciónRESUMEN
The ability to taste phenylthiocarbamide (PTC) has been investigated in a group of 366 Turkish medical students. The incidence of non-tasters was 7.78% (t gene frequency = .279) and 12.9% (t gene frequency = .359) for females and males respectively. The frequency of non-tasters for both sexes combined was 11.2% (t gene frequency = .335).