RESUMO

Mixed gonadal dysgenesis (MGD) includes a group of heterogeneous conditions consisting of a dysgenetic testis with a streak gonad. MGD is probably due to a disturbance in testicular determination/differentiation. The objective of this study is to analyze the SRY gene in MGD patients. A molecular investigation was undertaken in sixteen patients with this disorder in an attempt to determine mutations in SRY through polymerase chain reaction, single strand conformational polymorphism and direct sequencing. Eleven patients showed 45,X/46,XY and five 46,XY karyotype. Mutations in SRY gene were shown to be absent in these patients. This study confirms the findings of other studies. The etiology of MGD is heterogeneous, and cytogenetics mosaicism typically seen in these patients may be a cause of this condition, although, the presence of mutations in testicular organizing genes downstream of SRY is still to rule out.

Assuntos

RESUMO

Mixed gonadal dysgenesis (MGD) is an abnormality of sexual differentiation (ASD), which encompasses an heterogeneous group of different gonadal and phenotypic abnormalities. This study describes the main clinical features found in 16 patients with MGD, relating the clinical presentation with cytogenetic evaluation and histopathological findings. For purpose of this study, MGD was considered in those patients who fulfilled the following diagnostic criteria: 1) müllerian and/or wolfflan derivatives; 2) any of the following gonadal characteristics: a) bilateral intrabdominal or scrotal immature testicular tissue; b) intrabdominal or scrotal immature testicular tissue with contralateral streak gonad. Patients were selected from an ASD study which was carried out in Medical Genetic Unit of University of Zulia (UGM-LUZ), Maracaibo, Venezuela, from 1980 to 1997. The following information was extracted from the medical history at UGM-LUZ: age, gender which patient was reared, clinical presentation, cytogenetic evaluation, laparoscopic findings and gonadal biopsy. Sixteen patients fulfilled the diagnostic criteria and ranged in age from 1.2 to 39.4 years with an average of 12.65 years. Only 5 patients were reared as males. Twelve patients consulted for genital ambiguity. Chromosomal evaluation was as following: 8 patients with 45,X/46,XY mosaicism: 5 had a 46,XY normal male karyotype and the remaining patients: 46,XX; 46,XX/46,XY and 45,X/46,Xi(Xq) karyotypes, respectively. All patients showed müllerian derivatives and occasionally wolffian derivatives. Gonadal tumors were present in 2 patients. Molecular studies of genes that govern gonadal development are necessary for a better understanding of the wide heterogeneity present in MGD.

Assuntos

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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.

Assuntos

RESUMO

Mixed gonadal dysgenesis includes a heterogeneous group of different chromosomal, gonadal, and phenotypic abnormalities, characterized by the presence of a testis on one side and streak or an absent gonad on the other, persistence of müllerian duct structures and/or wolffian derivatives, and a variable degree of genital ambiguity. Here, we describe a patient with virilized external genitalia and phenotypic features of Turner syndrome, whose blood karyotype was 45,X/46,X,i(Xq). The presence of a unilateral dysgenetic testis was confirmed by histopathology. Using fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based analysis to detect Y-specific sequences, Y-chromosome material was not detected. To date, this is the first case reported of Xq-isochromosome associated with the presence of testicular tissue.

Assuntos

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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.

Assuntos

RESUMO

Abnormalities of sexual differentiation (ASD) represent a group of entities, heterogeneous in their etiopathogenesis and clinical manifestations. In order to characterize and analyze the epidemiologic, clinical, endocrine and genetic aspects of patients with ASD consulting UGM-LUZ between 1971-1996, the families that had at least one of its members affected were evaluated. Strict diagnostic criteria to each entity were applied. Cytogenetic, hormonal, radiological, echographic and anatomopathological evaluations were done in each patient. From 391 families, 429 patient consulted with ASD. They represent 5.4% of the patient who consulted to UGM-LUZ in the same period. 214 (50%) patients with definitive diagnosis of ASD were identified to fill the established inclusion criteria. The distribution was the following: 139 with anomalies of the sexual chromosomes; 36 with congenital adrenal hyperplasia; 21 with complete androgen insensitivity syndrome; 14 with mixed gonadal dysgenesis; and 4 with true hermaphroditism. 183 (42.7%) patients with male pseudohermaphroditism and 17 (3.9%) with female pseudohermaphroditism were diagnosed as they did not fulfill the established diagnostic criteria. 15 (3.4%) patients presented ASD associated to a polymalformative syndrome. The ASD are very complex entities, they need the participation of an interdisciplinary team for their diagnosis and management process.

PIP: 429 patients in 391 families consulted the Medical Genetics Unit of the University of Zulia in Maracaibo, Venezuela, from 1971 through 1996 concerning disorders of sexual differentiation. Strict diagnostic criteria were established for each condition. Each patient underwent a cytogenetic study of the peripheral blood, hormonal determinations, ultrasound diagnosis, and anatomic studies. Patients consulting for disorders of sexual differentiation represented 5.4% of all patients in the study period. 214 patients (50%) received definitive diagnoses of disorders of sexual differentiation. 139 received diagnoses of sex chromosome abnormalities, 36 had congenital adrenal hyperplasia, 21 had complete androgen insensitivity syndrome, 14 had mixed gonadal dysgenesis, and 4 had true hermaphrodism. 183 patients (42.7%) had male pseudohermaphrodism and 17 had female pseudohermaphrodism, but did not satisfy the established diagnostic criteria. 15 (3.4%) had disorders of sexual differentiation associated with polymalformative profiles. The disorders represented a significant cause of morbidity in the Medical Genetics Unit. Because of the complexity of the problem, such cases require the services of an integrated multidisciplinary health team.

Assuntos

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In 1964, Pfeiffer described a syndrome consisting of craniosynostosis, broad thumbs, broad great toes, and partial soft tissue syndactyly of the hands and feet. It belongs to acrocephalosyndactyly syndromes. We describe a male baby product of an eighth full-term uncomplicated uncontrolled pregnancy, mother and father normal and unrelated, 32 and 50 years old, respectively. He had all diagnostic and prognostic criteria of Subtype 2 Pfeiffer's Syndrome. The clinical, radiological, tomographic, and genetic aspects are discussed.

Assuntos

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Complete Androgen Insensitivity Syndrome (CAIS) is a type of Male Pseudohermaphroditism due to a defect in the androgen receptor which is a DNA-binding, transcription-regulating protein whose properties are induced on androgen binding. This defect is caused by mutations of a gene localized in Xq11-12. The objective of this study is the description of the clinical and pathological features of patients with female phenotype, karyotype 46, XY and diagnosis of CAIS. They were referred to Medical Genetic Unit of University of Zulia, Maracaibo, Venezuela, between 1971-1995. The diagnostic criteria and clinical and pathological findings are reviewed. Twenty-three patients fulfilled the diagnostic criteria. Most of patients were 13 years old or older (postpuberal). The main reasons for consultation were: primary amenorrhea, inguinal hernia, familial history of CAIS and fusion of labia minora. Seventeen patients from 5 families were diagnosed with CAIS and only one per family in 6 families. All patients showed a female general phenotype with unambiguously female external genitalia. Gonadal localization (right/left) was as follows: abdominal/abdominal: 65%; abdominal/inguinal: 26%; inguinal/abdominal: 9%. Histologic features of gonads were similar to those in cryptorchid testes of otherwise normal males. There was no evidence of development of gonadal neoplasia. The patients reported here provide a remarkable opportunity to study the molecular genetic characterization that can serve as a primary tool for diagnosis and subsequent therapy.

Assuntos

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Werner in 1915, described a patient is characterized by a tibial bilateral aplasia or hypoplasia, polydactyly and absent thumbs. Autosomal dominant inheritance is demonstrated, with variable expressivity. The objective of this work is to describe a child with clinic and radiologic signs of Tibial Hypoplasia with Polydactyly. The genealogic study allowed us to suppose that the gene has a variable expressivity, since in the maternal branch, malformations such as syndactyly of hands, proximal implantation of thumbs and tibiae vara, have been found. The clinic, radiologic, and genetic aspects are discussed.

Assuntos