RESUMO
Mixed gonadal dysgenesis is the most common chromosomal abnormality with ambiguous genitalia, defined as a 45,X/46,XY mosaicism. It can present with a normal male phenotype, ambiguous genitalia, or features of Turner syndrome. A 14-year-old patient was referred to the genetics clinic due to hypospadia, cryptorchidism, and aortic coarctation. During the physical examination, short stature, webbed neck, and Blashko lines on his back were noted. He had a previous karyotype reported as normal. However, due to an inadequate evolution and a low resolution on the previous test, a higher resolution karyotype was performed, identifying a mosaicism 45,X/46,XY. A multidisciplinary board examined the case, and follow-up with tumor markers was carried out to evaluate the presence of gonadoblastoma, one of the main complications in these patients. Treatment should be transdisciplinary and focused on the particular characteristics of each case. Other treatment alternatives include corrective surgery and hormonal therapy.
Assuntos
Transtornos do Desenvolvimento Sexual , Disgenesia Gonadal Mista , Síndrome de Turner , Feminino , Disgenesia Gonadal Mista/diagnóstico , Disgenesia Gonadal Mista/genética , Disgenesia Gonadal Mista/patologia , Humanos , Masculino , Mosaicismo , Fenótipo , Síndrome de Turner/complicações , Síndrome de Turner/diagnóstico , Síndrome de Turner/genéticaRESUMO
This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age due to atypical genitalia. He presented a right streak gonad, which was removed due to the risk for germ cell tumor, and a left testis with epididymis barely connected and without vas deferens. Left testis maintenance was sufficient for him to undergo spontaneous puberty. The patient was non-responsive to growth hormone. Webbed neck was the only dysmorphic feature. To the best of our knowledge, there were no similar cases reported with spontaneous pubertal progress reported in the literature.
Assuntos
Disgenesia Gonadal Mista/genética , Mosaicismo , Puberdade/genética , Adolescente , Humanos , Cariotipagem , MasculinoRESUMO
SUMMARY A gonadal tumor was diagnosed in the first months of life in a patient with genital ambiguity, a 45,X/46,XY karyotype, and mixed gonadal dysgenesis. Gonadal biopsies at the age of 3 months revealed dysgenetic testes and a gonadoblastoma on the right testis. Even though gonadal tumors are rare in childhood, this case indicates that prophylactic removal of dysgenetic gonads should be performed as early as possible, especially when the female sex is assigned to a patient with a Y-chromosome sequence.
Assuntos
Humanos , Masculino , Feminino , Lactente , Neoplasias Testiculares/patologia , Gonadoblastoma/patologia , Disgenesia Gonadal Mista/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/etiologia , Testículo/patologia , Biópsia , Fatores de Risco , Resultado do Tratamento , Gonadoblastoma/cirurgia , Gonadoblastoma/etiologia , Disgenesia Gonadal Mista/cirurgia , Disgenesia Gonadal Mista/complicaçõesRESUMO
A gonadal tumor was diagnosed in the first months of life in a patient with genital ambiguity, a 45,X/46,XY karyotype, and mixed gonadal dysgenesis. Gonadal biopsies at the age of 3 months revealed dysgenetic testes and a gonadoblastoma on the right testis. Even though gonadal tumors are rare in childhood, this case indicates that prophylactic removal of dysgenetic gonads should be performed as early as possible, especially when the female sex is assigned to a patient with a Y-chromosome sequence.
Assuntos
Disgenesia Gonadal Mista/patologia , Gonadoblastoma/patologia , Neoplasias Testiculares/patologia , Biópsia , Feminino , Disgenesia Gonadal Mista/complicações , Disgenesia Gonadal Mista/cirurgia , Gonadoblastoma/etiologia , Gonadoblastoma/cirurgia , Humanos , Lactente , Masculino , Fatores de Risco , Neoplasias Testiculares/etiologia , Neoplasias Testiculares/cirurgia , Testículo/patologia , Resultado do TratamentoRESUMO
La diferenciación sexual es un proceso genéticamente determinado y controlado, que puede ser alterado por diferentes tipos de mutaciones genéticas, o por el efecto de hormonas u otros disruptores ambientales que actúan sobre el embrión, resultando en la formación de genitales externos que no se corresponden con el sexo genético y con los genitales internos. La disgenesia gonadal mixta clasifica en los desórdenes de la diferenciación sexual de causa cromosómica. Se describe un paciente de un año de edad que es atendido en el Hospital Pediátrico “Juan Manuel Márquez”, por presentar genitales externos atípicos. El diagnóstico del paciente fue de disgenesia gonadal mixta, y se realizó con los complementarios siguientes: ecografía ginecológica, estudios hormonales y cariotipo. El tratamiento instaurado inicialmente, fue quirúrgico en dos tiempos operatorios, y el seguimiento hormonal hasta la pubertad (14 años), cuando se inició terapia de reemplazo hormonal según lo establecido por la edad de la paciente.
Sex differentiation is a genetically determined and controlled process that may be altered by various types of genetic mutations or by the effect of hormones or other environmental disruptors acting upon the embryo. The result is the formation of external genitalia that does not match with the genetic sex and the internal genitalia. Mixed gonadal dysgenesis is classified into the sexual differentiation disorders of chromosomal cause. Here is a one-year old child, who was seen at “Juan Manuel Marquez” pediatric hospital since he presented with atypical external genitalia. The diagnosis was mixed gonadal dysgenesis, based on supplementary tests like gynecological echography, hormone studies and karyotype. The initial treatment was surgical in two surgical times, and the hormonal follow-up lasted till puberty (14 years) when the hormone replacement therapy started according to the indications for the patient's age.
Assuntos
Humanos , Feminino , Diferenciação Sexual/genética , Disgenesia Gonadal Mista/cirurgia , Disgenesia Gonadal Mista/diagnóstico , Cromossomos SexuaisRESUMO
OBJECTIVE: To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. SUBJECTS AND METHODS: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. RESULTS: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. CONCLUSIONS: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/patologia , Hibridização in Situ Fluorescente , Mosaicismo , Mucosa Bucal , Adolescente , Adulto , Núcleo Celular , Criança , Pré-Escolar , Transtornos do Desenvolvimento Sexual/sangue , Feminino , Disgenesia Gonadal 46 XY/sangue , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal Mista/sangue , Disgenesia Gonadal Mista/genética , Humanos , Infertilidade Masculina/genética , Interfase , Linfócitos , Masculino , Síndrome de Turner/genética , Adulto JovemRESUMO
Objetivo: Verificar se a hibridização in situ por fluorescência (FISH) em células de mucosa oral poderia ser empregada para detectar criptomosaicismo com linhagem 45,X em pacientes 46,XY. Sujeitos e métodos: Amostra de 19 jovens saudáveis 46,XY e cinco pacientes com distúrbios da diferenciação do sexo (DDS), quatro 45,X/46,XY e um 46,XY. FISH com sondas específicas para X e Y em núcleos interfásicos de linfócitos e mucosa oral para investigar a proporção de núcleos contendo apenas o sinal do cromossomo X. Resultados: A frequência de núcleos contendo apenas o sinal do X nos dois tecidos dos homens saudáveis não diferiu (p = 0,69). Em todos os pacientes com DDS essa frequência foi significativamente maior, e também não houve diferença entre os dois tecidos (p = 0,38). Conclusões: A investigação de mosaicismo com linhagem 45,X em pacientes com DDS 46,XY ou esterilidade pode ser feita por FISH diretamente em células de mucosa oral. .
Objective: To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium. .
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/patologia , Hibridização in Situ Fluorescente , Mosaicismo , Mucosa Bucal , Núcleo Celular , Transtornos do Desenvolvimento Sexual/sangue , /sangue , /genética , Disgenesia Gonadal Mista/sangue , Disgenesia Gonadal Mista/genética , Interfase , Infertilidade Masculina/genética , Linfócitos , Síndrome de Turner/genéticaRESUMO
FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51.
FISH tem sido usado como um complemento para a citogenética clássica na detecção de mosaicismo em anomalias de cromossomos sexuais. O objetivo deste trabalho é descrever três casos nos quais o diagnóstico final só foi obtido por meio de FISH. O caso 1 é uma menina de 8 anos, 46,XY, com genitália feminina normal, encaminhada ao nosso setor devido à baixa estatura. A análise de linfócitos por FISH com sondas centroméricas de X e Y identificou a constituição 45,X/46,X,idic(Y) e estabeleceu o diagnóstico de síndrome de Turner. O caso 2 é um menino de 21 meses, 46,XY, com ambiguidade genital (hipospadia peniana, testículo à direita e gônada disgenética à esquerda). FISH de linfócitos e mucosa oral identificou o cariótipo 45,X/46,XY, levando ao diagnóstico de disgenesia gonadal mista. O caso 3 é um rapaz de 19 anos, 47,XYY, com atraso de desenvolvimento neuromotor, dificuldade de aprendizado, problemas psicológicos, alta estatura, testículos pequenos, gonadotrofinas elevadas e azoospermia. FISH de linfócitos e mucosa oral identificou a constituição 47,XYY/48,XXYY. Os casos 1 e 2 ilustram a variabilidade fenotípica do mosaico 45,X/46,XY e a importância da detecção da linhagem 45,X na avaliação e na condução dos casos. No caso 3, a função gonadal anormal pôde ser explicada pela linhagem 48,XXYY. O uso de FISH na prática clínica é particularmente relevante quando a análise citogenética clássica traz resultados normais ou incertos em pacientes com quadro sugestivo de uma aneuploidia de cromossomos sexuais. Arq Bras Endocrinol Metab. 2012;56(8):545-51.
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Disgenesia Gonadal Mista/diagnóstico , Hibridização in Situ Fluorescente/métodos , Mosaicismo , Aberrações dos Cromossomos Sexuais , Síndrome de Turner/diagnóstico , Disgenesia Gonadal Mista/genética , Síndrome de Turner/genéticaRESUMO
FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy.
Assuntos
Disgenesia Gonadal Mista/diagnóstico , Hibridização in Situ Fluorescente/métodos , Mosaicismo , Aberrações dos Cromossomos Sexuais , Síndrome de Turner/diagnóstico , Criança , Pré-Escolar , Feminino , Disgenesia Gonadal Mista/genética , Humanos , Masculino , Síndrome de Turner/genética , Adulto JovemRESUMO
Conceitualmente, as gônadas disgenéticas são gônadas que não sofreram uma completa diferenciação. Em vista disso, constituem parte de uma ampla gama de entidades clínicas possuidoras de fenótipos e de genótipos diversos. Seus cariótipos contêm o cromossomo Y ou seus fragmentos, ou raramente não os contêm. Essas alterações geram maior risco para a ocorrência de neoplasias nessas gônadas. Na sequência deste estudo apresentamos as neoplasias mais comumente associadas aos diversos tipos de disgenesias gonadais. A neoplasia mais comum é o gonadoblastoma e outros como os disgerminomas e os tumores do seio endodérmico também podem estar associados. A detecção dessas anormalidades de modo precoce é o que nos motivou para a presente revisão
By definition, dysgenetic gonads are those that did not undergo a complete differentiation. They make up a vast array of clinical entities, having different phenotypes and genotypes. Their kariotypes contain the Y chromosome or fragments of it, and, in rare cases, do not contain it. Such alterations generate greater potential for the occurrence of neoplasms in such gonads. This study presents neoplasms which are most commonly associated with several types of gonadal dysgenesis. The most common neoplasia is gonadoblastoma and others like disgerminoma or yolk sac tumors may be associated. The early detection of such potential is the reason for this review
Assuntos
Humanos , Masculino , Feminino , Células Germinativas/patologia , Disgenesia Gonadal/complicações , Disgerminoma/etiologia , Gonadoblastoma/etiologia , Tumor do Seio Endodérmico/etiologia , Disgenesia Gonadal Mista , Gônadas/anormalidades , Síndrome de TurnerRESUMO
BACKGROUND: The potential involvement of SRY in abnormal gonadal development in 45,X/46,X,der(Y) patients was proposed following the identification of SRY mutations in a few patients with Turner syndrome (TS). However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified. AIMS: it was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45,X/46,X,der(Y) karyotype. PATIENTS: twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis (MGD), harboring 45,X/46,X,der(Y) karyotypes were selected. METHODS: Genomic DNA was extracted from peripheral blood leukocytes of all patients and from gonadal tissue in 4 cases. The SRY coding region was PCR amplified and sequenced. RESULTS: We identified only 1 polymorphism (c.561CâT) in a 45,X/46,XY MGD patient, which was detected in blood and in gonadal tissue. CONCLUSION: our results indicate that mutations in SRY are rare findings in patients with Y chromosome mosaicisms. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45,X/46,XY karyotype and variants seems very unlikely.
Assuntos
Disgenesia Gonadal Mista/etiologia , Disgenesia Gonadal Mista/genética , Mutação , Proteína da Região Y Determinante do Sexo/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , Mosaicismo , Polimorfismo de Nucleotídeo Único , Síndrome de Turner/etiologia , Síndrome de Turner/genéticaRESUMO
The objective of this study was to describe the change in diagnosis and prognosis of a child with testicular dysgenesis and 46,XY karyotype after detection of a 45,X cell line and to discuss the difficulties caused by the terms mixed gonadal dysgenesis (MGD) and XY partial gonadal dysgenesis (XYPGD). One case was reported including clinical and laboratory findings of a child of 41-day-old infant with 1.3-cm phallus, penoscrotal hypospadias and left prepubertal testis. Karyotype 46,XY (16 cells), normal hormone levels. Right streak gonad, epididymis and müllerian remnants were removed; initial diagnosis was XYPGD. Persistent growth retardation led to further cytogenetic analysis (50 cells) and detection of a 45,X cell line. Detection of a 45,X lineage changed both the diagnosis to MGD and also the prognosis.The number of cells analyzed in karyotyping is critical. Use of MGD and XYPGD to designate both a histological picture and a syndromic diagnosis, results in lack of emphasis on clinical differences between 46,XY and 45,X/46,XY subjects.
Assuntos
Disgenesia Gonadal 46 XY/patologia , Disgenesia Gonadal Mista/patologia , Fenótipo , Testículo/patologia , Diagnóstico Diferencial , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal Mista/genética , Humanos , Lactente , Masculino , Prognóstico , Testículo/anormalidadesRESUMO
The objective of this study was to describe the change in diagnosis and prognosis of a child with testicular dysgenesis and 46,XY karyotype after detection of a 45,X cell line and to discuss the difficulties caused by the terms mixed gonadal dysgenesis (MGD) and XY partial gonadal dysgenesis (XYPGD). One case was reported including clinical and laboratory findings of a child of 41-day-old infant with 1.3-cm phallus, penoscrotal hypospadias and left prepubertal testis. Karyotype 46,XY (16 cells), normal hormone levels. Right streak gonad, epididymis and müllerian remnants were removed; initial diagnosis was XYPGD. Persistent growth retardation led to further cytogenetic analysis (50 cells) and detection of a 45,X cell line. Detection of a 45,X lineage changed both the diagnosis to MGD and also the prognosis.The number of cells analyzed in karyotyping is critical. Use of MGD and XYPGD to designate both a histological picture and a syndromic diagnosis, results in lack of emphasis on clinical differences between 46,XY and 45,X/46,XY subjects.
O objetivo deste trabalho foi descrever a mudança no diagnóstico e no prognóstico de criança com disgenesia testicular e cariótipo 46,XY após detecção de linhagem 45,X e discutir as dificuldades causadas pelas denominações disgenesia gonadal mista (DGM) e disgenesia gonadal parcial XY (DGPXY). Relatou-se um caso incluindo achados clínicos e laboratoriais de uma criança de 41 dias com falo de 1,3 cm, hipospadia penoescrotal e testículo pré-puberal à esquerda. Cariótipo 46,XY (16 células), níveis hormonais normais. Gônada direita (disgenética), epidídimo e remanescentes müllerianos foram removidos; o diagnóstico inicial foi DGPXY. Retardo de crescimento persistente levou à ampliação da análise citogenética (50 células) e à detecção de linhagem 45,X. A detecção de linhagem 45,X modificou o diagnóstico para DGM e também o prognóstico. No cariótipo, o número de células analisadas é crítico. O uso de DGM e DGPXY para designar tanto quadro histológico quanto diagnóstico clínico resulta em falta de ênfase nas diferenças clínicas entre indivíduos 46,XY e 45,X/46,XY.
Assuntos
Humanos , Lactente , Masculino , /patologia , Disgenesia Gonadal Mista/patologia , Fenótipo , Testículo/patologia , Diagnóstico Diferencial , /genética , Disgenesia Gonadal Mista/genética , Prognóstico , Testículo/anormalidadesRESUMO
Ring chromosomes are present in 1 in 25,000 human fetuses; 99% arise de novo while less than 1% of rings are inherited. This chromosomal rearrangement may arise through a cytogenetic mechanism involving breaks in chromosome arms and fusion of the proximal broken ends, leading to a loss of distal material. Most patient Y ring chromosomes are present in a 45,X/46,X,r(Y) mosaic karyotype; molecular analyses of infertile men have shown that it is not rare to find r(Y) in these patients. However, the clinical spectrum in those cases with a 45,X cell line is broad and depends on the percentage of the monosomic cell line in different tissues. Y chromosome abnormalities and 45,X mosaic karyotypes are often associated with disorders of sex determination. Here, we report a male patient with hypospadias, cryptorchidism and a mosaic karyotype containing a low proportion of 45,X monosomic cells and multiple ring Y chromosomes in peripheral blood. Clinical, surgical, and molecular evidence was sufficient for a diagnosis of mixed gonadal dysgenesis. We suggest that a detailed cytogenetic and molecular analysis should be done in all males with bilateral descended testes and infertility.
Assuntos
Cromossomos Humanos Y/genética , Disgenesia Gonadal Mista/genética , Mosaicismo , Cromossomos em Anel , Núcleo Celular/metabolismo , Centrômero/metabolismo , Criança , Bandeamento Cromossômico , Humanos , Hibridização in Situ Fluorescente , Interfase , Cariotipagem , Masculino , Metáfase , Fenótipo , Proteína da Região Y Determinante do Sexo/metabolismoRESUMO
Gonadoblastoma (GB) is an in situ tumor consisting of a heterogeneous population of mature and immature germ cells, other cells resembling immature Sertoli/granulosa cells, and Leydig/lutein-like cells, may also be present. GB almost exclusively affects a subset of patients with intersex disorders and in 30% of them overgrowth of the germinal component of the tumor is observed and the lesion is term dysgerminoma/seminoma. Several pathways have been proposed to explain the malignant process, and abnormal OCT3/4 expression is the most robust risk factor for malignant transformation. Some authors have suggested that OCT3/4 and beta-catenin might both be involved in the same oncogenic pathway, as both genes are master regulators of cell differentiation and, overexpression of either gene may result in cancer development. The mechanism by which beta-catenin participates in GB transformation is not completely clear and exploration of the E-cadherin pathway did not conclusively show that this pathway participated in the molecular pathogenesis of GB. Here we analyze seven patients with mixed gonadal dysgenesis and GB, in an effort to elucidate the participation of beta-catenin and E-cadherin, as well as OCT3/4, in the oncogenic pathways involved in the transformation of GB into seminoma/dysgerminoma. We conclude that the proliferation of immature germ cells in GB may be due to an interaction between OCT3/4 and accumulated beta-catenin in the nuclei of the immature germ cells.
Assuntos
Caderinas/fisiologia , Disgerminoma/etiologia , Disgenesia Gonadal Mista/complicações , Gonadoblastoma/etiologia , Fator 3 de Transcrição de Octâmero/fisiologia , Neoplasias Ovarianas/etiologia , Neoplasias Testiculares/complicações , beta Catenina/fisiologia , Adolescente , Transformação Celular Neoplásica , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , MasculinoRESUMO
A higher incidence of Y-chromosome microdeletions was found on gonadal DNA than on peripheral blood lymphocyte DNA and on streak gonads than on dysgenetic testis in 11 patients with 45,X/46,XY gonadal dysgenesis. It is probable that an association between Y-chromosome microdeletions and severity of the phenotype in 45,X/46,XY patients exists.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Y , Disgenesia Gonadal Mista/genética , Gônadas/metabolismo , DNA/análise , Feminino , Frequência do Gene , Disgenesia Gonadal Mista/metabolismo , Humanos , Masculino , MosaicismoRESUMO
Se presenta el caso de una paciente de 14 años y ocho meses, referida a la consulta por presentar amenorrea, talla baja y estigmas turnerianos al examen físico. El cariotipo realizado en sangre periférica y gónadas, así como el perfil endocrinológico y el resultado histopatológico de las gónadas fueron fundamentales para establecer el diagnóstico diferencial con disgenesia gonadal mixta. Se indicó terapia de reemplazo hormonal con estrógenos equinos conjugados presentando buena evolución clínica
Assuntos
Feminino , Humanos , Adolescente , Transtornos do Desenvolvimento Sexual , Disgenesia Gonadal Mista , Síndrome de Turner/diagnóstico , Síndrome de Turner/sangue , Venezuela , Ginecologia , ObstetríciaRESUMO
Gonadoblastoma is an unusual mixed germ cell-sex cord-stromal tumor that has the potential for malignant transformation and 30% of all patients with gonadoblastoma develop germ cell tumors mainly dysgerminoma/seminoma. An additional 10% gives rise to other malignant germ cell neoplasms. This tumor affects a subset of patients with intersex disorders. The age at diagnosis is variable ranging from birth to the fourth decade, but around 94% of cases are diagnosed during the first three decades of life and there are few cases with gonadoblastoma diagnosed in infants. In this paper, we present the histological and molecular findings of four patients with gonadal dysgenesis who developed gonadoblastoma in the first 2 years of life and one case with bilateral dysgerminoma diagnosed at 15 years of age. The sex chromosomes of mosaic patients do not distribute homogenously in dysgenetic gonads; however, statistical analysis of FISH results revealed significant differences between the XY cell line in the gonadoblastoma compared with the dysgenetic testis. Our cases demonstrate that tumors could be present at a very early age, so the prophylactic removal of the gonads is advised.
Assuntos
Cromossomos Humanos Y/genética , Disgenesia Gonadal Mista/genética , Gonadoblastoma/patologia , Neoplasias Ovarianas/patologia , Neoplasias Testiculares/patologia , Testículo/anormalidades , Adolescente , Pré-Escolar , Feminino , Disgenesia Gonadal Mista/patologia , Gonadoblastoma/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Neoplasias Ovarianas/genética , Neoplasias Testiculares/genéticaRESUMO
OBJECTIVE: To investigate the presence of mutations in the open reading frame (ORF), as well as on the 5' and 3', flanking regions of the SRY gene in patients with mixed gonadal dysgenesis (MGD) or with Turner syndrome (TS) and Y mosaicism. STUDY DESIGN: We studied 13 patients with MGD and three patients with TS and Y mosaicism. DNA was isolated from blood leukocytes for subsequent polymerase chain reaction (PCR) and direct sequencing were performed in the ORF, as well as from the 5' and 3' flanking regions of the SRY gene. RESULTS: No mutations were present in any of the patients studied. CONCLUSION: The absence of mutations in these regions indicated that mutations were an unlikely cause of MGD or TS with Y mosaicism and suggested that there are others genes playing an important role in sex development.
Assuntos
Cromossomos Humanos Y/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Disgenesia Gonadal Mista/genética , Mosaicismo/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Síndrome de Turner/genética , Adolescente , Adulto , Criança , Pré-Escolar , DNA/sangue , Humanos , Lactente , Leucócitos/química , Masculino , Fases de Leitura Aberta/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Proteína da Região Y Determinante do SexoRESUMO
Se presentó una paciente con estigmas turnerianos y cariotipo 45,X/46,XX con diagnóstico inicial de síndrome de Turner a la que se le realizó clitoridectomía por hipertrofia del clítoris a los 8 meses de edad. Se reevaluó a los 6 años de edad y se le realizó cariotipo con técnicas de bandas G (GTG) con fórmula cromosómica de 45,X/46,X, (cromosoma marcador -mar); dicho marcador dio la impresión de una deleción del cromosoma X desde Xq13 ®Xq ter y Xp22 ®Xp ter. Se completó dicho estudio con técnica molecular de reacción en cadena de la polimerasa (PCR) y se identificó el gen SRY en el cromosoma marcador. Se realizó intervención quirúrgica por mínimo acceso y se comprobó ausencia de útero así como trompa en el lado derecho con ausencia de gónada y en el lado opuesto, testículo rudimentario; se planteó el diagnóstico de disgenesia gonadal mixta(AU)