Analysis of FMR1 gene CGG repeats among patients with diminished ovarian reserve / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between Fragile X mental retardation gene-1 (FMR1) gene CGG repeats with diminished ovarian reserve (DOR).@*METHODS@#For 214 females diagnosed with DOR, DNA was extracted from peripheral blood samples. FMR1 gene CGG repeats were determined by PCR and capillary electrophoresis.@*RESULTS@#Three DOR patients were found to carry FMR1 premutations, and one patient was found to carry gray zone FMR1 repeats. After genetic counseling, one patient and the sister of another patient, both carrying FMR1 permutations, conceived naturally. Prenatal diagnosis showed that both fetuses have carried FMR1 permutations.@*CONCLUSION@#FMR1 gene permutation may be associated with DOR. Determination of FMR1 gene CGG repeats in DOR patients can provide a basis for genetic counseling and guidance for reproduction.

Amenorrea primaria asociada a paciente con cariotipo 45 XX, ROB (13; 14) (q 10; q 10): presentación de un caso / Primary amenorrhea associated with a patient with karyotype 45 XX, ROB (13; 14) (q 10; q 10): case presentation

La función ovárica depende de la expresión de múltiples genes, por lo que las anomalías del cromosoma X y los autosomas revisten gran importancia en la etiología de la insuficiencia ovárica primaria (IOP). Las translocaciones de autosomas en mujeres con IOP son muy raras y solo se han detectado tres casos: dos translocaciones entre los cromosomas 2 y 15 en dos mujeres con cariotipo 46, XX, t (2, 15) (q32.3, q13.3)2; una translocación entre los cromosomas 13 y 14 en una mujer con cariotipo 45, XX, t (13; 14)3; por lo que nuestro caso sería el cuarto reporte de mujeres con translocaciones de autosomas e IOP.

Ovarian function depends on the expression of multiple genes, so Xchromosome abnormalities and autosomes are of great importance in the etiology of primary ovarian insufficiency (IOP). Autosomal translocations in women with IOP are very rare and only three cases have been detected: two translocations between chromosomes 2 and 15 in two women with karyotype 46, XX, t (2, 15) (q32.3, q13.3)2; a translocation between chromosomes 13 and 14 in a woman with karyotype 45, XX, t (13; 14)3 , so our case would be the fourth report of women with autosomal translocations and IOP.

How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency / Como os marcadores polimórficos contribuem para as doenças genéticas em diferentes populações? O estudo da inibina A para insuficiência ovariana prematura

ABSTRACT Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

RESUMO Objetivo Verificar a incidência da mutação G679A no éxon 2 do gene da inibina alfa (INHA) em mulheres com amenorreia secundária e diagnóstico de insuficiência ovariana prematura e em controles. Métodos Uma amostra de 5mL de sangue periférico foi coletada de todos os participantes do estudo em tubo de EDTA e utilizada para a extração de DNA. Para o grupo de pacientes, foram coletados também 5mL de sangue em tubo contendo heparina para realização de cariótipo, e 5mL um tubo seco para dosagem de hormônio folículo-estimulante. As amostras de pacientes e controles foram inicialmente submetidas à análise da variante G679A no éxon 2 do gene INHA pela técnica de PCR-RFLP. As amostras de pacientes com insuficiência ovariana prematura após PCR-RFLP foram submetidas ao sequenciamento de Sanger dos éxons codantes 2 e 3. O sequenciamento foi realizado em equipamento ABI 3500 GeneticAnalyzer, e os resultados foram avaliados pelos programas SeqA and Variant Reporter. Resultados Foram avaliadas amostras de 70 mulheres com insuficiência ovariana prematura e de 97 controles férteis. A variante G769A foi encontrada em apenas uma paciente do Grupo Insuficiência Ovariana Prematura e em nenhum controle, e parece ser rara nas pacientes brasileiras com insuficiência ovariana prematura. Este polimorfismo foi previamente associado à insuficiência ovariana prematura em diversas populações no mundo. Conclusão O estudo evidenciou que há heterogeneidade genética quanto ao INHA em diferentes populações e entre as causas de insuficiência ovariana prematura.

Tremor-Ataxia syndrome and primary ovarian insufficiency in an FMR1 premutation carrier / Síndrome de Tremor Ataxia y falla ovárica prematura en portadora de la premutación del gen FMR1

Abstract Introduction: The FMR1 gene has four allelic variants according to the number of repeats of the CGG triplet. Premutation carriers with between 55 and 200 repeats are susceptible to developing pathologies such as tremor and ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) syndrome. Case description: The patient was a 53-year-old female farmer with severe tremor in the upper limbs at rest that worsens with movement, tremor in the jaw and tongue, and generalized cerebral atrophy. She is a carrier of the FMR1 premutation diagnosed by PCR and Southern Blot, complying with the clinical and radiological criteria of FXTAS, and in addition, has a history of vagal symptoms suggestive of ovarian failure and menstrual cycle disorders that led to hysterectomy at age 33 and was subsequently diagnosed with FXPOI. Conclusion: An unusual case of FXTAS and FXPOI complying with clinical and radiological criteria is reported in a premutation carrier of the FMR1 gene.

Resumen Introducción: el gen FMR1 tiene cuatro variantes alélicas según el número de repeticiones de la tripleta CGG. Los portadores de la premutación con un número entre 55 y 200 repeticiones son susceptibles de desarrollar patologías como el síndrome de temblor y ataxia (FXTAS) y síndrome de falla ovárica prematura (FXPOI) asociados al X frágil. Descripción del caso: Mujer de 53 años, agricultora, con temblor severo en miembros superiores en reposo que empeora con el movimiento, temblor en mandíbula y lengua, atrofia cerebral generalizada, portadora de la premutación del gen FMR1 diagnosticada por PCR y Southern Blot, cumpliendo con criterios clínicos y radiológicos de FXTAS; ademas, historia de síntomas vagales sugestivos de falla ovárica y trastornos del ciclo menstrual que llevaron a histerectomía a los 33 años, haciendose diagnóstico FXPOI. Conclusión: Se reporta un caso inusual en portadoras de la premutación del gen FMR1, con criterios clínicos y radiológicos de FXTAS y FXPOI.

Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure

OBJECTIVES: Primary ovarian failure is a rare disorder, and approximately 90% of cases are of unknown etiology. The aim of this study was to search for mutations in NANOS3, a gene that was recently related to the etiology of primary ovarian failure, in a group of Brazilian women. METHODS: We screened for NANOS3 DNA variants in 30 consecutive women who were previously diagnosed with primary ovarian failure, of unknown etiology and compared the results with those from 185 women with normal fertility. The NANOS3 gene was amplified by polymerase chain reaction using pairs of specific primers and then sequenced. The resulting sequences were compared with control sequences available in the National Center for Biotechnology and Information database. RESULTS: No mutations in NANOS3 were found in primary ovarian failure patients, but four previously described polymorphisms were identified at a similar frequency in the control and primary ovarian failure groups. CONCLUSIONS: Mutations in NANOS3 were not associated with primary ovarian failure in the present cohort.

Chromosomal abnormalities & oxidative stress in women with premature ovarian failure (POF).

Background & objectives: Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 yr and is characterized by amenorrhoea, hypoestrogenism and elevated serum gonadotrophin levels. The cause of POF remains undetermined in majority of the cases. This study was aimed to investigate the type and frequency of cytogenetic abnormalities in patients with idiopathic POF and also to study the role of oxidative stress in such cases. Methods: Seventy five women with idiopathic POF were included in this study. Chromosome analysis was done in peripheral blood lymphocytes by conventional GTG banding to identify numerical or structural abnormalities. Cytogenetically normal cases were investigated for reactive oxygen species (ROS) levels in their blood by luminol-chemiluminescence assay. Results: Eighteen chromosomal anomalies were identified in POF patients (24%). Majority of the cases were found to have X-chromosome abnormalities (28%). Overall median ROS range was found to be significantly higher (P<0.01) in POF patients [50480 (120,132966) RLU/min] compared to controls [340 (120,5094) RLU/min]. Among these, 50 per cent of the POF patients had higher ROS levels, 20 per cent had medium elevation and 30 per cent were found to have normal values comparable to controls. Interpretation & conclusions: X-chromosome anomalies were found to be the major contributor of POF. Oxidative stress may be the underlying aetiology in idiopathic premature ovarian failure. Thus the results of this study highlight the role of cytogenetic abnormalities and supraphysiological levels of ROS in causation of idiopathic POF. But the role of oxidative stress needs to be confirmed by other studies on patients from different geographical areas and from different ethnicities.

Bases genéticas del síndrome de ovarios poliquísticos / Genetic bases of polycystic ovary syndrome

El síndrome de ovarios poliquísticos es el trastorno endocrino que más afecta la esfera reproductiva de la mujer en la edad fértil, sus causas se desconocen con exactitud, pero la mayoría de los expertos coinciden en plantear que es una entidad multifactorial, en la que los factores genéticos cada vez cobran mayor importancia. En los últimos años se han identificado varios genes involucrados en los procesos patogénicos de este síndrome, y dentro de estos, los más importantes son aquellos que codifican para enzimas de la esteroidogénesis, para el receptor de insulina y otras hormonas relacionadas con la acción de la insulina, así como las gonadotropinas y sus receptores, aspectos sobre los cuales trata la siguiente revisión(AU)

The syndrome of polycystic ovaries is the endocrine disorder involving more the reproductive sphere of the woman in fertile age, its causes are unknown with accuracy, but most of experts coincide in propose that it is a multifactor entity where the genetic factor more and more have a great significance. In past years, it has been possible to identify some genes involved in the pathogenic processes of this syndrome and among the more important are included those codifying for enzymes of the steroidogenesis, for the insulin receptor and other hormones related to the insulin action, as well as the gonadotropins and its receptors, features that are the aim of present review(AU)

Falência ovariana prematura: aspectos genéticos / Premature ovarian failure: genetic aspects

A falência ovariana prematura exige, para avaliação conveniente dos diversos fenômenos etiológicos envolvidos, adequada análise de seus fatores causais. Entre as possíveis causas genéticas, encontram-se anomalias gênicas ou cromossômicas, seja nos cromossomos X ou nos autossomos. O presente estudo apresenta, de modo sucinto, revisão dos fatores genéticos que são responsáveis por tais fenômenos etiológicos.

Premature ovarian failure demands a proper analysis of countless factors for an accurate assessment of the several etiological phenomena processes involved. Among the possible genetic causes, it has been detected genic of chromossomal anomalies, ocurring either on the sex chromosomes or on the autosomes. This study presents a review of the genetic and chromosomal factors which account for etiological phenomena.

Estudios de la región 5'UTR del gen FMR-1 en pacientes con falla ovárica prematura / Studies of the 5' - UTRTR region in the FMR-1 gene in patients withe Premature Ovarian Failure

La falla ovárica prematura (FOP) es un síndrome de patogénesis multicausal que afecta aproximadamente al 1% de las mujeres en edad reproductiva. Numerosos estudios asocian el estado de premutación (amplificación del número de tripletes CGG entre 50/55 y 200 repeticiones) en el gen FMR-1 y FOP. Alrededor de un 4% de las pacientes FOP presentan alelos con premutación. La amplificación del número de tripletes por encima de 200 repeticiones causa el Síndrome de Fragilidad del X (SFX). El objetivo del presente trabajo fue estudiar la región 5´ no codificante del gen en un grupo de pacientes FOP de Argentina. La región de interés se amplificó por PCR a partir de muestras de ADN de 100 pacientes FOP y 145 mujeres controles. Los alelos de las pacientes y controles fueron agrupados en 7 categorías de acuerdo al número de tripletes obtenidos. Se observó que el número de repeticiones más frecuente se encuentra en el rango de 26 a 30 tripletes, tanto en pacientes como en controles. En el grupo de pacientes FOP, 5/197 (2.6%) alelos no relacionados estudiados presentaron un número de tripletes CGG mayor a 50, mientras que sólo 1 de 290 (0.34%) para el grupo control. Todas las pacientes FOP con valores de tripletes CGG mayor a 50 presentaron amenorrea secundaria. Estos resultados están en concordancia con lo comunicado para otras poblaciones acerca de la existencia de una asociación entre la premutación del gen FMR-1 y el desarrollo de FOP. Asimismo, los resultados obtenidos refuerzan la importancia de la genotipificación del gen FMR-1 en las pacientes FOP, a los efectos de estimar el riesgo de su descendencia para el SFX.

Premature ovarian failure (POF) is a syndrome of multicausal pathogenesis that affects 1% of women before the age of 40. Several studies associate the premutation state (CGG repeats increased in number between 50/55 and 200) in the FMR-1 gene and POF. About 4% of POF women have alleles in the FMR-1 gene in the permutation range. An increase above 200 in the number of triplets in this gene causes the Fragile X Syndrome (FXS). The purpose of the present study was to analyze the 5´untranslated region of the FMR-1 gene in a group of patients from Argentina. The region of interest was amplified by PCR from DNA samples of 100 POF patients and 145 control women. Alleles from controls and patients were grouped in 7 categories according to the number of triplets obtained. We observed that the most frequent number of repeats ranged from 26 to 30 triplets, in both patient and control groups. In the POF group, 5 out of 197 (2.6%) not related alleles presented a number of CGG triplets higher than 50, while only 1 out of 290 (0.34%) was present in controls. All POF patients with a number of CGG repeats higher than 50 presented secondary amenorrhea. These results are in accordance with previous reports from other populations showing an association between the premutation state in the FMR-1 gene and POF development. In addition, these results reinforce the importance of genotyping POF patients to estimate the risk of their offspring for Fragile X Syndrome.

Falla ovárica precoz: [revisión] / Premature ovarian failure: [review]

La falla ovárica precoz es una amenorrea secundaria que se presenta en una mujer antes de los 40 años, que conlleva a hipoestrogenismo, infertilidad y las consecuencias de la menopausia prematura, como osteoporosis, enfermedad cardiovascular, trastornos neurovegetativos, entre otros. Se presenta agotamiento folicular, por dotación insuficiente de folículos o destrucción acelerada de los ovocitos. Las causas son varias, pero predominan las genéticas, autoinmunes y las iatrogénicas. Entre las causas genéticas, son frecuentes las deleciones Xq y Xp, las translocaciones, aberraciones numéricas (47,XXX, 45,X0), premutaciones de X frágil, entre otros. Entre las enfermedades autoinmunes son de importancia la insuficiencia poliglandular tipo I y II. Las iatrogenias pueden ser quirúrgicas en ovarios o trompas y, con la presencia del cáncer de mama en mujeres jóvenes, el tratamiento oncológico puede destruir las células germinales, por lo que hoy se sugiere utilizar técnicas de preservación de la función ovárica y de la fertilidad. En el manejo de la falla ovárica precoz, una vez determinada la causa, se sugiere el uso de terapia estrogénica, aunque no se ha hecho investigación en el tipo de hormona a utilizar, dosis y consecuencias a largo plazo. Tener presente la prevención y manejo de la osteoporosis y la enfermedad cardiovascular. Con relación a la infertilidad, se está realizando criopreservación de embriones y ovocitos para autodonación, así como criopreservación de tejido ovárico cortical para autotrasplante posterior, con éxitos y limitaciones. Los agonistas de GnRH podrían actuar en proteger los ovarios en casos de quimioterapia. Se observa con atención la terapia génica experimental en casos de falla ovárica precoz.

Premature ovarian failure is characterized by secondary amenorrhea affectinga woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberrations (47,XXX, 45,X0), fragil X premutations are frequent. Type I and type II poliglandular insufficiency are important causes among autoimmune diseases. Iatrogenia may occur in surgery of the ovaries and Fallopian tubes and with oncologic treatment that destroys germinal cells in young women with breast cancer. Nowadays use of ovarian function and fertility preservation techniques are suggested. Once the cause is determined estrogens use is recommended although little research on hormone type, dosage and long term consequences has been done. Care must be placed in osteoporosis and cardiovascular disease prevention and treatment. In regards to infertility, there is already experience with embryos and oocytes cryopreservation for autodonation, and cortical ovarian tissue cryopreservation for posterior autotrasplantation, with success as well as limitations. GnRH agonists could protect the ovaries when chemotherapy is used. Attention is placed on experimental gene therapy in cases of premature ovarian failure.

Falla ovárica precoz / Premature ovarian failure

La falla ovárica precoz es una amenorrea secundaria que se presenta en una mujer antes de los 40 años, que conlleva a hipoestrogenismo, infertilidad y las consecuencias de la menopausia prematura, como osteoporosis, enfermedad cardiovascular, trastornos neurovegetativos, entre otros. Se presenta agotamiento folicular, por dotación insuficiente de folículos o destrucción acelerada de los ovocitos. Las causas son varias, pero predominan las genéticas, autoinmunes y las iatrogénicas. Entre las causas genéticas, son frecuentes las deleciones Xq y Xp, las translocaciones, aberraciones numéricas (47,XXX, 45,X0), premutaciones de X frágil, entre otros. Entre las enfermedades autoinmunes son de importancia la insuficiencia poliglandular tipo I y II. Las iatrogenias pueden ser quirúrgicas en ovarios o trompas y, con la presencia del cáncer de mama en mujeres jóvenes, el tratamiento oncológico puede destruir las células germinales, por lo que hoy se sugiere utilizar técnicas de preservación de la función ovárica y de la fertilidad. En el manejo de la falla ovárica precoz, una vez determinada la causa, se sugiere el uso de terapia estrogénica, aunque no se ha hecho investigación en el tipo de hormona a utilizar, dosis y consecuencias a largo plazo. Tener presente la prevención y manejo de la osteoporosis y la enfermedad cardiovascular. Con relación a la infertilidad, se está realizando criopreservación de embriones y ovocitos para autodonación, así como criopreservación de tejido ovárico cortical para autotrasplante posterior, con éxitos y limitaciones. Los agonistas de GnRH podrían actuar en proteger los ovarios en casos de quimioterapia. Se observa con atención la terapia génica experimental en casos de falla ovárica precoz

Premature ovarian failure is characterized by secondary amenorrhea affectinga woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberrations (47,XXX, 45,X0), fragil X premutations are frequent. Type I and type II poliglandular insufficiency are important causes among autoimmune diseases. Iatrogenia may occur in surgery of the ovaries and Fallopian tubes and with oncologic treatment that destroys germinal cells in young women with breast cancer. Nowadays use of ovarian function and fertility preservation techniques are suggested. Once the cause is determined estrogens use is recommended although little research on hormone type, dosage and long term consequences has been done. Care must be placed in osteoporosis and cardiovascular disease prevention and treatment. In regards to infertility, there is already experience with embryos and oocytes cryopreservation for autodonation, and cortical ovarian tissue cryopreservation for posterior autotrasplantation, with success as well as limitations. GnRH agonists could protect the ovaries when chemotherapy is used. Attention is placed on experimental gene therapy in cases of premature ovarian failure

Existence of inhibin alpha-subunit gene mutation in a population of Iranian women with premature ovarian failure

Premature ovarian failure [POF] is characterized by hypergonadotropic amenorrhea, before the age of 40, for which the Inhibin alpha-submit [INH alpha] gene is proposed as a candidate gene, due to its role in negative feedback control of FSH. In this study we aimed at demonstrating the candidate mutation as a gene variation associated with POF in Iranian population. Using DNA sequencing, DNA samples of 24 women with POF and 24 controls aged below 40 years, were screened for mutations in the Inhibin gene. The 769G[right wards arrow] A mutation in exon 2 of the Inhibin alpha gene was found in four out of 24 idiopathic POF patients. The results obtained in this study have shown that this variation is more frequent in patients with POF than in normal fertile populations of Iran

Falência ovariana prematura: aspectos atuais / Premature ovarian failure: present aspects

A falência ovariana prematura (FOP) acomete aproximadamente 1:1000 mulheres antes dos 30 anos, 1:250 em torno dos 35 anos e de 1:100 aos 40 anos. Manifesta-se como amenorréia primária ou amenorréia secundária, não podendo ser considerada definitiva em todas as pacientes, uma vez que a concepção espontânea pode ocorrer em até 5-10 por cento das FOP. Na maioria dos casos apresenta-se na forma esporádica, pois apenas 5 por cento apresentam história familial. Entre as causas conhecidas estão as alterações cromossômicas, dos genes ligados ao cromossomo X e cromossomos autossômicos, doenças autoimunes, alterações tóxicas e iatrogênicas. Com relativa freqüência, a causa etiológica não é obtida, sendo então denominada de idiopática. O diagnóstico da FOP é feito baseado na história clínica e níveis elevados do hormônio folículo estimulante (FSH), sendo posteriormente investigadas as causas mais específicas. O manejo clínico visa o suporte emocional, o tratamento hormonal com estrogênios e progestogênios, a abordagem da infertilidade e a prevenção de co-morbidades como a osteoporose e potencial maior risco cardiovascular.

Premature ovarian failure occurs in approximately 1:1000 women before 30 years, 1:250 by 35 years and 1:100 by the age of 40. It is characterized by primary or secondary amenorrhea and cannot be considered as definitive because spontaneous conception may occur in 5 to 10 percent of cases. In 95 percent of cases, premature ovarian failure is sporadic. The known causes of premature ovarian failure include chromosomal defects, autoimmune diseases, exposure to radiation or chemotherapy, surgical procedures, and certain drugs. Frequently, however, the etiology is not clear and these cases are considered to be idiopathic. Premature ovarian failure is defined by gonadal failure and high serum follicle-stimulating hormone (FSH) levels. Clinical approach includes emotional support, hormonal therapy with estrogens and progesterone or progestogens, infertility treatment, and prevention of osteoporosis and potential cardiovascular risk.

G769A Variation of Inhibin alpha -gene in Korean Women with Premature Ovarian Failure

Premature ovarian failure (POF) is menopause before the age of 40 years. The frequency of POF is about 1% of all women. Recently inhibin alpha gene (INHalpha) has been indicated as candidate in POF pathogenesis. Inhibin, a glycoprotein, is a gonadal hormone, which can inhibit the synthesis and secretion of pituitary follicle-stimulating hormone (FSH), which has an important role in the recruitment and development of ovarian follicles during the folliculogenesis. G769A variation of INH alpha, alanine, is highly conserved across species, and has an important role of its receptor binding. We screened a G769A transition in the INHalpha from the total population of the patients of 84 women with POF and 100 normal fertile women. We found no variation between the normal subjects and the POF patients. G769A variation of INHalpha is rare in Korea women with POF.

Falla ovárica prematura familiar / Premature ovarian failure family

Relata-se quatro pacientes de duas famílias, com falência ovariana prematura (FOP) de caráter familiar, sendo que em uma delas as afetadas eram irmäs monozigóticas. O distúrbio se apresentou em três geraçöes em uma família (duas irmäs, mäe e avó materna); também se observou mulheres com outros transtornos da funçäo ovariana nestas famílias. O cariótipo foi normal nas 4 pacientes e näo achou nenhuma outra enfermidade genética ou auto-imune nelas. As características gerais e as manifestaçöes clínicas foram similares às da FOP esporádica. A via de transmissäo da FOP foi por via materna em uma família e por via paterna em outra, possivelmente com caráter autossômico dominante limitada pelo sexo ou dominante ligada ao cromossoma X. Enfatiza-se a importância de avaliar a história menstrual e reprodutiva dos familiares maternos e paternos, assim como a recomendaçäo de concepçäo precoce a outra mulheres destas famílias, já que há um fator de risco.

Cytogenetic study of women with premature ovarian failure

A etiologia da insuficiência ovariana prematura (POF) ainda é desconhecida na maioria dos pacientes. Uma vez que alguns casos estäo associados a anormalidades do cromossomo X, estudamos citogeneticamente pacientes portadores de POF. Comparamos as culturas de linfócitos de onze pacientes com as de indivíduos controle de mesmas idades. Todos os indivíduos estudados apresentaram cariótipos normais. As freqüências de células aneuplóides e com aberraçöes cromossômicas estruturais näo diferiram entre os grupos. Verificamos uma maior freqüência de aneuploidia e de divisäo prematura do centrômero do cromossomo X nos dois grupos.

True 47,XXX in a patient with premature ovarian failure: the first reported case in Thailand.

A case of triple-X female with premature ovarian failure was reported. The patient was a 23-year-old, single, Thai woman who presented with primary amenorrhea, incomplete development of the secondary sex characteristics, elevated levels of serum gonadotropins, and decreased estrogen concentration. Immunological abnormalities were not identified by antinuclear antibody, rheumatoid factor, antimicrosomal antibody and antithyroglobulin antibody studies. Cyclic estrogen-progestin was given and withdrawal bleeding occurred. The present case represents the utilization of chromosomal analysis in a patient with delayed sexual development, or primary amenorrhea and elevated serum gonadotropin levels.

Citogenética de la falla ovárica prematura / Citogenetics of early ovarian failure

La falla ovárica prematura se define por la ocurrencia de la menopausia antes de los 40 años. Entre las etiologías se describen factores genéticos, autoinmunes, infecciosos, resistencia a gonadotrofinas y otros. Cuarenta y siete pacientes con este diagnóstico fueron referidos a estudio citogenético. En un 68% de los casos se encontró un cariotipo normal. En un 10,7% había una sola célula alterada 45,X y se diagnosticó como normal. En un 15% de las pacientes se observó un mosaico de células normales y otras líneas 45,X, 47,XXX y 48,XXXX. Dos mujeres tenían una constitución cromosómica 47,XXX. En una paciente de 22 años se observó una translocación recíproca balanceada 46,X t(X;18) (q21,1;q22). La presencia de diversas líneas celulares, con mosaicos conteniendo mitosis 45,X podría explicar una pérdida acelerada de gametos a nivel ovárico. En mujeres con cariotipo 47,XXX puede haber compromiso de la fertilidad y se ha descrito menopausia precoz. El estudio de la translocación balanceda X-autosoma con técnicas de DNA podría dilucidar la base molecular de la falla ovárica, permitiendo una búsqueda dirigida del gen en el sitio de disrrupción