[Cytogenetic findings in ductal carcinoma of the breast]. / Hallazgos citogenéticos en carcinoma ductal de mama.

Breast cancer in women is an important medical problem with public health and social implications. In spite of its great clinical importance, little is known about the cytogenetic features of breast carcinomas. Chromosomal abnormalities in some malignant tumors have been used for diagnosis and prognosis or for localizing genes involved in the pathology malignancies. In this report, we present the chromosomal abnormalities found in 32 primary breast ductal carcinomas. The tumor samples were studied using the technique for short-term culturing and cytogenetic analysis with G-banding. Only one tumor with normal karyotype was observed. Thirty one (99%) of the tumors had chromosomal abnormalities including 21 (65.6%) in which chromosome 1 was involved (trisomy, monosomy or structural abnormalities of the type t(1q;2p) and del(1q42). Other recurrent anomalies such as del(12p); del 4(p); +7; +8; -7; -3; were observed. The significance of these findings and their role in tumorogenesis will become more evident with close follow-up of women who have tumors with an abnormal karyotype.

[Clonal chromosome abnormalities in malignant hematological diseases using fluorescence in situ hybridization]. / Anormalidades cromosómicas clonales en enfermedades hematológicas malignas mediante FISH.

Fluorescent in situ hybridization (FISH) is a rapid, sensitive and reliable method for the identification of complete chromosomes, or segments of them, during metaphase or nuclear interphase. The present study shows the results of the analysis of 32 bone marrow aspirates from patients with malignant hematological diseases (11 AML, 7 ALL, 12 CML and 2 CLL), referred to the Medical Genetics Unit of the Faculty of Medicine, Zulia University, Maracaibo, Venezuela between 1994 and 1996. All samples were studied by conventional and molecular techniques (FISH), using probes of total chromosomes, alpha-satellites and locus specific. In patients with AML and ALL and FISH technique detected clonal chromosomal abnormalities, that were not found by the conventional cytogenetic technique. Furthermore, the PML-alpha RARA complex was identified in the promyelocytic acute leukemias. The presence of the molecular complex ABL-BCR was also demonstrated in CML. The present study demonstrates the usefulness of the FISH technique in the detection of clonal chromosomal abnormalities, which are important when considering the clinical care of patients with these pathologies.

[Prenatal diagnosis. I: Prenatal diagnosis program at the Medical Genetics Unit of the Universidad de Zulia, Maracaibo, Venezuela]. / Diagnóstico prenatal. I: Programa de diagnóstico prenatal de la Unidad de Genética Médica de La Universidad del Zulia, Maracaibo, Venezuela.

The Prenatal Diagnosis Program of the Medical Genetic Unit of University of Zulia has the following objectives: Identification of Genetic Risk Factors (GRF) in those couples who attend to the Prenatal Genetic Clinic, application of different prenatal diagnostic procedures (PDP), and providing adequate genetic counseling. The goal of this paper is to show preliminary results obtained between January 1993 and December 1996. Three hundred and twenty one pregnant women were analyzed by determining the GRF and taking into account the genetic clinical history. The GRF analyzed were: Advanced maternal age (AMA), congenital malformation history (CMH), previous child with chromosomic anomalies (PCCA), defects of neural tube history (DNTH), congenital heart disease history (CHDH), any parent carrier of chromosomic anomaly (PCA), habitual abortion (HA), abnormal fetal echography (AFE), altered maternal serum levels of alpha-feto-protein (AMSAFP) and OTHERS: exposure to teratogenic agents, history of Mendelian diseases, maternal systemic diseases and anxiety in the mother or in her partner. The PDP was designed according to the GRF, which included fetal echography (FE), fetal echocardiography (FEc), amniocentesis (AMN), chordocentesis (CCT) and AMSAFP. Results showed that 58.4% of the expectant mothers asked for counseling during the 2nd trimester, 70% of the total showed only one GRF, and AMA was the most frequent GRF found (40.3%), followed by PCCA, AFE, CHDH, HA, DNTH, PCA, and OTHERS in that order. The specific PDP applied to the identified GRF allowed a health evaluation of the fetus. The GRF identification gave the opportunity of establishing a Prenatal Diagnostic Program producing a response to the couple's needs and showed the utility of an integral and multidisciplinary management directed to any expecting mother in order to identify any high GRF.

[Chronic myeloid leukemia. Karyotype changes]. / Leucemia mieloide crónica. Evolución en el cariotipo.

Chronic Myeloid Leukemia (CML) is a clonal disease of bone marrow, citogenetically characterized by the presence of the Philadelphia chromosome (Ph). Additional anomalies in the Ph cromosome have been found during the evolution of CML. This paper will show evidence of cytogenetic abnormalities during the evolution of CML in this region, and its correlation with clinical evolution. 55 samples of bone marrow, 81.3% (45/55) in chronic phase (CP), 12.7% (7/55) in an accelerated phase (AP), and 5.4% (3/55) in blastic phase (BP) were received. In 12/45 patients in CP the karyotype was repeated at least once a year during the evolution of their illness. 9/12 presented the Ph chromosome as a single anomaly at the moment of diagnosis; the other 3 presented a distinct anomaly. 4/9 presented additional abnormalities moving to the stages AP or BP between 4-8 months after initial discovery. 7/10 patients referred in AP or BP presented additional abnormalities in the Ph chromosome. It is evident that the chromosome study of each patient with CML must be carried out at least once a year in order to detect chromosomal abnormalities in addition to the Ph chromosome. Thus, a greater therapeutic control of the disease is possible.

[Hereditary diseases and congenital malformations at the Unit of Medical Genetics of the University of Zulia. Years: 1983-1992]. / Enfermedades hereditarias y malformaciones congénitas en la Unidad de Genética Médica de la Universidad del Zulia. Años: 1983-1992.

The Medical Genetics Unit at Universidad del Zulia (UGM-LUZ) gives counsel to patients with partial and total genetic diseases. Counseling is available for patients of both sexes and all ages, from public and private health centers and several medical specialities. In the present study an analysis of 4617 clinical records from families referred for genetic counseling to the UGM-LUZ is given. The study spans from January 1983 to December 1992. Fifty four (1.2%) of these histories correspond to pre-nuptial counseling, 773 (16.7%) pre-conceptional, 316 (6.8%) pre-natal and 3474 (75.3%) for diagnosis. A computerized system was developed, based on relational data base manager, that permits access with interactive Dbase type applications. A total of 5433 diagnoses were made. The most frequent causes of genetic diseases were chromosomal abnormalities (12.32%), mainly Down and Turner syndromes. Mendelian diseases occupied 14.45% of all cases, with Marfan and Noonan syndrome, Osteogenesis imperfecta. Duchenne-Becker muscular dystrophy and Incontinentia Pigmenti as the most frequent syndromes. Diseases that involve multifactorial inheritance, such as neural tube defects, accounted for 7.36% of all diagnosis. Effects of teratogenic agents such as german measles, radiations and others were detected in 3.96% of all cases. In 8.5% of the patients a hereditary factor was suspected. No definitive diagnosis was reached in 32.45% of all cases and 20.96% of the patients were normal. The need for data from other medical genetic centers is stressed. In this way the regional and national genetic diseases on morbidity can be known.

Clinical experience with balanced reciprocal translocations.

Clinical experience with balanced reciprocal translocations: In order to evaluate past experience with respect to the occurrence of balanced reciprocal translocations (BRT) in patients with malformation syndromes and/or mental retardation (MS/MR) and in couples with reproductive failure, 4,335 karyotypes from the Genetics Unit of the Universidad del Zulia from January 1971 to December 1994 were reviewed, resulting in the identification of 15 cases of BRT (0.34%). All BRT were classic (CT) according to the number of breakpoints. In 66.6% of the cases, the indication for chromosome analysis was a MS/MR; 20% reproductive failure and, in 13.3% the BRT was a fortuitous finding. BRT were of familial origin in 6/15 (40%), 3/15 (20%) were de novo and the other 6/15 (40%) were of unknown origin. It was concluded that BRT can affect the phenotype, particularly when the request for the karyotype is motivated by MS/MR, and that genetic counseling in individuals at risk to be carrier is indicated.

[Application of the high resolution chromosomic technic in patients in high risk of cytogenetic anomalies]. / Aplicación de la técnica de Alta Resolución Cromosómica en pacientes con alto riesgo para anomalías citogenéticas.

Since the beginning of cytogenetics, there has been a constant improvement of chromosomal culture and banding techniques. In 1976, Yunis described a high chromosomal resolution technique (HRC), that permits the detection of subtle chromosomal abnormalities. The present work, reports the results obtained when HRC was applied to the study of chromosomal abnormalities in patients with high risk of such. The study comprised 434 specimens of venous blood and 182 bone marrow aspirates. The samples were classified according to the presuntive diagnoses. The highest frequency of chromosomal abnormalities, was found in blood samples from patients with physical deformities with or without mental retardation (22.22%), followed by mental retardation autism and/or fragile X chromosome (13.66%), and in couples with reproductive disorders (5.8%). In bone marrow, the most frequent abnormalities corresponded to patients with chronic myeloid leukemia (78.43%), acute lymphocytic leukemia (62.10%), acute myeloide leukemia (61.9%), myelodisplastic syndromes (43.7%) and chronic lymphocytic leukemia (14.2%). The present results stress the need to apply the HRC technique when the probability of minute chromosomal abnormalities is high.

[Significance of chromosome changes in chronic myeloid leukemia]. / Importancia de las alteraciones cromosómicas en la leucemia mieloide crónica.

Chronic myelocytic leukemia is a particular subtype of leukemia characterized by increased myeloid precursor cells. It has been associated with the presence of the Philadelphia chromosome, described by Nowel and Hungerford in 1960, as a deletion of part of the long arm of a G group chromosome, the 22 chromosome. The present work reports the chromosomal abnormalities observed in 39 patients with chronic myelocytic leukemia, studied at the Genetic Unit, in the Faculty of Medicine of Zulia University, during the period from 1987 to 1991. Sixty per cent of the patients showed different abnormalities, such as 8 trisomy, t (8;22), and in the remaining 15%, no chromosomal changes were detected. The patients with t (9;22) as the only abnormality, had less relapses and longer survival. The clinical course of 50% of the patients with normal karyotype was similar to those with t (9;22) as the only abnormality; the other 50% had an accelerated course with frequent relapses and early death. The present findings confirm that the presence of the Philadelphia chromosome as the only karyotypical abnormality, is indicative of better prognosis, and its association with other chromosomal changes predicts a more accelerated course that will probably require a more aggressive treatment.