The Experts below are selected from a list of 840 Experts worldwide ranked by ideXlab platform
Juan Pablo Méndez - One of the best experts on this subject based on the ideXlab platform.
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DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete Pure Gonadal Dysgenesis.
Molecular and cellular endocrinology, 2008Co-Authors: Irene Sánchez-moreno, Patricia Canto, Edgardo Reyes, Patricia Munguía, Mario Bermúdez De León, Bulmaro Cisneros, Felipe Vilchis, Juan Pablo MéndezAbstract:Mutations of SRY are the cause of 46,XY complete Pure Gonadal Dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded Gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C muta- tion, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to Gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY com- plete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity. © 2008 Elsevier Ireland Ltd. All rights reserved.
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Mutations in the Desert hedgehog (DHH) Gene in Patients with 46,XY Complete Pure Gonadal Dysgenesis
The Journal of clinical endocrinology and metabolism, 2004Co-Authors: Patricia Canto, Daniela Söderlund, Edgardo Reyes, Juan Pablo MéndezAbstract:Mutations of SRY are the cause of complete Pure Gonadal Dysgenesis (PGD) in 10-15% of patients. In the remaining individuals, it has been suggested that mutations in other genes involved in the testis-determining pathway could be causative. We describe the first report in which three cases of 46,XY complete PGD are attributed to mutations of the Desert hedgehog (DHH) gene. DHH was sequenced using genomic DNA from paraffin-embedded Gonadal tissue from six patients with complete 46,XY PGD. Mutations were found in three patients: a homozygous mutation in exon 2, responsible for a L162P, and a homozygous 1086delG in exon 3. Mutated individuals displayed 46,XY complete PGD, differentiating from the only previously described patient with a homozygous DHH mutation, who exhibited a partial form of PGD with polyneuropathy, suggesting that localization of mutations influence phenotypic expression. This constitutes the first report where mutations of DHH are associated with the presence of 46,XY complete PGD, demonstrating that the genetic origin of this entity is heterogeneous and that disorders in other genes, different from SRY, involved in the testis-determining pathway are implicated in abnormal testicular differentiation in humans. These data extend previous reports demonstrating DHH is a key gene in Gonadal differentiation.
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No evidence of mutations in the follicle-stimulating hormone receptor gene in Mexican women with 46,XX Pure Gonadal Dysgenesis.
American journal of medical genetics, 2001Co-Authors: Elsa De La Chesnaye, Patricia Canto, Alfredo Ulloa-aguirre, Juan Pablo MéndezAbstract:In the ovary FSH is necessary for normal follicular development, binding to its receptor (FSHR) that pertains to the superfamily of G-protein coupled receptors. In the FSHR gene, which consists of 10 exons, an homozygous mutation was reported in six Finnish families with Gonadal Dysgenesis; whereas two isolated French patients exhibited compound heterozygous mutations. Several groups, however, have searched for FSHR mutations, although in most cases the gene has been studied partially, not finding any genetic abnormalities in German, English, North American or Brazilian women. We performed direct sequencing of all 10 exons of the FSHR gene in seven sporadic patients and two sisters with 46,XX Pure Gonadal Dysgenesis, to investigate the cause of their disorder. No heterozygous or homozygous mutant alleles were present in any of the patients. Although the number of patients evaluated was small, considering all the other previous reports, it seems that except in the Finnish population, the proportion of women with mutations in the encoding region of this gene is very low. Other possibilities for the presence of 46,XX Gonadal Dysgenesis, such as defects in the regulatory regions of the FSHR gene promoter, in the untranslated regions of exons 1 and 10, and within introns, or the existence of other genes likely to be important for normal ovarian function on the X chromosome or on autosomes, should be considered. In contrast with other studies, we did not find polymorphisms of the FSHR gene, indicating that apparently in Mexicans this gene is not highly polymorphic.
A Sato - One of the best experts on this subject based on the ideXlab platform.
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Dysgerminoma with syncytiotrophoblastic giant cells arising from 46,XX Pure Gonadal Dysgenesis.
Obstetrics and gynecology, 1998Co-Authors: Y Morimura, H Nishiyama, K Yanagida, A SatoAbstract:Dysgerminoma with syncytiotrophblastic giant cells is a rare ovarian tumor. Only ten cases of this tumor have been reported, and all tumors developed in normal ovaries. This report presents a case of dysgerminoma with syncytiotrophoblastic giant cells arising in a patient with 46,XX Pure Gonadal Dysgenesis. An 18-year-old phenotypic female of normal height without somatic anomalies with nonfunctional ovaries underwent a bilateral gonadectomy for a right ovarian tumor and left streak gonad. The tumor revealed a dysgerminoma containing scattered syncytiotrophoblastic giant cells. Her serum hCG was elevated, and hCG was demonstrated within syncytiotrophoblastic giant cells immunohistochemically. The clinical diagnosis was stage Ia dysgerminoma with syncytiotrophoblastic giant cells. Her karyotype was 46,XX and the sex-determining region Y gene was not detected in tumor DNA by polymerase chain reaction analysis. This rare Gonadal tumor may arise from dysgenetic gonads in addition to gonadoblastoma and Pure dysgerminoma. It is an example of tumorgenesis in Pure Gonadal Dysgenesis with no identifiable Y chromosome component.
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Dysgerminoma with syncytiotrophoblastic giant cells arising from 46,xx Pure Gonadal Dysgenesis
Obstetrics & Gynecology, 1998Co-Authors: Y Morimura, H Nishiyama, K Yanagida, A SatoAbstract:Abstract Background: Dysgerminoma with syncytiotrophblastic giant cells is a rare ovarian tumor. Only ten cases of this tumor have been reported, and all tumors developed in normal ovaries. This report presents a case of dysgerminoma with syncytiotrophoblastic giant cells arising in a patient with 46,XX Pure Gonadal Dysgenesis. Case: An 18-year-old phenotypic female of normal height without somatic anomalies with nonfunctional ovaries underwent a bilateral gonadectomy for a right ovarian tumor and left streak gonad. The tumor revealed a dysgerminoma containing scattered syncytiotrophoblastic giant cells. Her serum hCG was elevated, and hCG was demonstrated within syncytiotrophoblastic giant cells immunohistochemically. The clinical diagnosis was stage Ia dysgerminoma with syncytiotrophoblastic giant cells. Her karyotype was 46,XX and the sex-determining region Y gene was not detected in tumor DNA by polymerase chain reaction analysis. Conclusion: This rare Gonadal tumor may arise from dysgenetic gonads in addition to gonadoblastoma and Pure dysgerminoma. It is an example of tumorgenesis in Pure Gonadal Dysgenesis with no identifiable Y chromosome component.
Yuji Taketani - One of the best experts on this subject based on the ideXlab platform.
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Y Ghromosome Analysis and Laparoscopic Surgery in XY Pure Gonadal Dysgenesis: A Case Report and a Review of Literature
Asia-Oceania journal of obstetrics and gynaecology, 2010Co-Authors: Osamu Tsutsumi, Taku Iida, Yuji Taketani, Naomi Hakuno, Miyuki Sadatsuki, Takashi Okai, Shigeo Nagafuchi, Yutaka NakahoriAbstract:DNA analysis and laparoscopic surgery were performed on a patient with 46, XY Pure Gonadal Dysgenesis. Southern-blot and polymerase chain-reaction analyses revealed that she had no apparent deletion of the Y chromosome, including the SRY gene (sex-determining region Y), suggesting that the patient might have some other abnormality. Since the risk of Gonadal neoplasia in XY Gonadal dysplasia is high, operative laparoscopy was performed to ensure that there was no malignancy in the patient. Laparoscopic surgery is recommended because of the amount of the surgery and the rapid postoperative recovery of the patient.
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A case of XY Pure Gonadal Dysgenesis with 46,XYp-/47,XXYp- karyotype whose gonadoblastoma was removed laparoscopically.
Gynecologic and obstetric investigation, 2000Co-Authors: Yasushi Takai, Osamu Tsutsumi, Ikuko Harada, Yutaka Morita, Mikio Momoeda, Yoshimitsu Fukushima, Yuji TaketaniAbstract:A case of Pure Gonadal Dysgenesis was investigated. The patient was an 18-year-old Japanese woman with a history of primary amenorrhea. She had poorly developed breasts, a hypoplastic uterus, a normal vagina and infantile genitalia. The patient's karyotype was 46,XYp-/ 47,XXYp-. Microsatellite analysis revealed that the X chromosomes of this patient originated from one of the two maternal X chromosomes. DNA analysis of the Y chromosome revealed that she had a deletion of SRY (the sex-determining region on the Y chromosome). She underwent laparoscopic gonadectomies with a final pathology consistent with gonadoblastoma. Laparoscopic surgery is recommended as it is much less invasive and associated with rapid postoperative recovery.
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a case of xy Pure Gonadal Dysgenesis with 46 xyp 47 xxyp karyotype whose gonadoblastoma was removed laparoscopically
Gynecologic and Obstetric Investigation, 2000Co-Authors: Yasushi Takai, Osamu Tsutsumi, Ikuko Harada, Yutaka Morita, Mikio Momoeda, Yoshimitsu Fukushima, Yuji TaketaniAbstract:A case of Pure Gonadal Dysgenesis was investigated. The patient was an 18-year-old Japanese woman with a history of primary amenorrhea. She had poorly developed breasts, a hypoplastic uterus, a normal vagina and infantile genitalia. The patient's karyotype was 46,XYp-/ 47,XXYp-. Microsatellite analysis revealed that the X chromosomes of this patient originated from one of the two maternal X chromosomes. DNA analysis of the Y chromosome revealed that she had a deletion of SRY (the sex-determining region on the Y chromosome). She underwent laparoscopic gonadectomies with a final pathology consistent with gonadoblastoma. Laparoscopic surgery is recommended as it is much less invasive and associated with rapid postoperative recovery.
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Laparoscopic surgery and DNA analysis in patients with XY Pure Gonadal Dysgenesis.
Journal of obstetrics and gynaecology (Tokyo Japan), 1995Co-Authors: Osamu Tsutsumi, Taku Iida, Yuji TaketaniAbstract:The sex-determining region on the Y chromosome (SRY) encodes a gene that has many of the properties expected of the testis-determining factor. The XY Pure Gonadal Dysgenesis is characterized by streak gonads in phenotypic females who lack the somatic abnormalities and short stature associated with Turner's syndrome. Abnormalities within the SRY have been described in these patients. However, we have experienced several patients with short stature whose SRY are apparently normal. The DNA sequencing of the SRY gene showed a 100% nucleotide sequence identity with the reported cloned sequence. Sex reversal in two of the present cases may be due to mutation at a locus other than SRY in the sex determining pathway, a gene potentially involved in the determination of human constitution. The risk of developing malignancy in the dysgenetic gonads has been reported to be 25%, dictating early prophylactic removal of the streaks. Laparoscopic surgery is recommended because of the amount of the surgery and the rapid postoperative recovery of the patient.
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Intact Sex Determining Region Y (SRY) in a Patient with XY Pure Gonadal Dysgenesis and a Twin Brother.
Endocrine journal, 1994Co-Authors: Osamu Tsutsumi, Taku Iida, Yuji Taketani, Yutaka Nakahori, Motoyasu Sugase, Yasuo NakagomeAbstract:A patient with an apparently normal 46, XY karyotype, suffering from Pure Gonadal Dysgenesis and of short stature was investigated. The patient, who was growth retarded, was a 30-year-old married Japanese woman with a history of primary amenorrhea and infertility with a weight of 42 kg and a height of 146cm. She has a phenotypically and karyotypically normal dizygotic twin brother with normal development. Southern-blot and polymerase chain-reaction analyses revealed no apparent deletions in the patient's Y chromosome, including the sex-determining region Y (SRY). The DNA sequencing of the SRY gene showed a 100% nucleotide sequence identity with the reported cloned sequence. Sex reversal in the present case may be due to mutation at a locus other than SRY in the sex determining pathway, a gene potentially involved in the determination of human constitution.
Patricia Canto - One of the best experts on this subject based on the ideXlab platform.
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DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete Pure Gonadal Dysgenesis.
Molecular and cellular endocrinology, 2008Co-Authors: Irene Sánchez-moreno, Patricia Canto, Edgardo Reyes, Patricia Munguía, Mario Bermúdez De León, Bulmaro Cisneros, Felipe Vilchis, Juan Pablo MéndezAbstract:Mutations of SRY are the cause of 46,XY complete Pure Gonadal Dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded Gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C muta- tion, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to Gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY com- plete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity. © 2008 Elsevier Ireland Ltd. All rights reserved.
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Mutations in the Desert hedgehog (DHH) Gene in Patients with 46,XY Complete Pure Gonadal Dysgenesis
The Journal of clinical endocrinology and metabolism, 2004Co-Authors: Patricia Canto, Daniela Söderlund, Edgardo Reyes, Juan Pablo MéndezAbstract:Mutations of SRY are the cause of complete Pure Gonadal Dysgenesis (PGD) in 10-15% of patients. In the remaining individuals, it has been suggested that mutations in other genes involved in the testis-determining pathway could be causative. We describe the first report in which three cases of 46,XY complete PGD are attributed to mutations of the Desert hedgehog (DHH) gene. DHH was sequenced using genomic DNA from paraffin-embedded Gonadal tissue from six patients with complete 46,XY PGD. Mutations were found in three patients: a homozygous mutation in exon 2, responsible for a L162P, and a homozygous 1086delG in exon 3. Mutated individuals displayed 46,XY complete PGD, differentiating from the only previously described patient with a homozygous DHH mutation, who exhibited a partial form of PGD with polyneuropathy, suggesting that localization of mutations influence phenotypic expression. This constitutes the first report where mutations of DHH are associated with the presence of 46,XY complete PGD, demonstrating that the genetic origin of this entity is heterogeneous and that disorders in other genes, different from SRY, involved in the testis-determining pathway are implicated in abnormal testicular differentiation in humans. These data extend previous reports demonstrating DHH is a key gene in Gonadal differentiation.
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No evidence of mutations in the follicle-stimulating hormone receptor gene in Mexican women with 46,XX Pure Gonadal Dysgenesis.
American journal of medical genetics, 2001Co-Authors: Elsa De La Chesnaye, Patricia Canto, Alfredo Ulloa-aguirre, Juan Pablo MéndezAbstract:In the ovary FSH is necessary for normal follicular development, binding to its receptor (FSHR) that pertains to the superfamily of G-protein coupled receptors. In the FSHR gene, which consists of 10 exons, an homozygous mutation was reported in six Finnish families with Gonadal Dysgenesis; whereas two isolated French patients exhibited compound heterozygous mutations. Several groups, however, have searched for FSHR mutations, although in most cases the gene has been studied partially, not finding any genetic abnormalities in German, English, North American or Brazilian women. We performed direct sequencing of all 10 exons of the FSHR gene in seven sporadic patients and two sisters with 46,XX Pure Gonadal Dysgenesis, to investigate the cause of their disorder. No heterozygous or homozygous mutant alleles were present in any of the patients. Although the number of patients evaluated was small, considering all the other previous reports, it seems that except in the Finnish population, the proportion of women with mutations in the encoding region of this gene is very low. Other possibilities for the presence of 46,XX Gonadal Dysgenesis, such as defects in the regulatory regions of the FSHR gene promoter, in the untranslated regions of exons 1 and 10, and within introns, or the existence of other genes likely to be important for normal ovarian function on the X chromosome or on autosomes, should be considered. In contrast with other studies, we did not find polymorphisms of the FSHR gene, indicating that apparently in Mexicans this gene is not highly polymorphic.
Y Morimura - One of the best experts on this subject based on the ideXlab platform.
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Dysgerminoma with syncytiotrophoblastic giant cells arising from 46,XX Pure Gonadal Dysgenesis.
Obstetrics and gynecology, 1998Co-Authors: Y Morimura, H Nishiyama, K Yanagida, A SatoAbstract:Dysgerminoma with syncytiotrophblastic giant cells is a rare ovarian tumor. Only ten cases of this tumor have been reported, and all tumors developed in normal ovaries. This report presents a case of dysgerminoma with syncytiotrophoblastic giant cells arising in a patient with 46,XX Pure Gonadal Dysgenesis. An 18-year-old phenotypic female of normal height without somatic anomalies with nonfunctional ovaries underwent a bilateral gonadectomy for a right ovarian tumor and left streak gonad. The tumor revealed a dysgerminoma containing scattered syncytiotrophoblastic giant cells. Her serum hCG was elevated, and hCG was demonstrated within syncytiotrophoblastic giant cells immunohistochemically. The clinical diagnosis was stage Ia dysgerminoma with syncytiotrophoblastic giant cells. Her karyotype was 46,XX and the sex-determining region Y gene was not detected in tumor DNA by polymerase chain reaction analysis. This rare Gonadal tumor may arise from dysgenetic gonads in addition to gonadoblastoma and Pure dysgerminoma. It is an example of tumorgenesis in Pure Gonadal Dysgenesis with no identifiable Y chromosome component.
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Dysgerminoma with syncytiotrophoblastic giant cells arising from 46,xx Pure Gonadal Dysgenesis
Obstetrics & Gynecology, 1998Co-Authors: Y Morimura, H Nishiyama, K Yanagida, A SatoAbstract:Abstract Background: Dysgerminoma with syncytiotrophblastic giant cells is a rare ovarian tumor. Only ten cases of this tumor have been reported, and all tumors developed in normal ovaries. This report presents a case of dysgerminoma with syncytiotrophoblastic giant cells arising in a patient with 46,XX Pure Gonadal Dysgenesis. Case: An 18-year-old phenotypic female of normal height without somatic anomalies with nonfunctional ovaries underwent a bilateral gonadectomy for a right ovarian tumor and left streak gonad. The tumor revealed a dysgerminoma containing scattered syncytiotrophoblastic giant cells. Her serum hCG was elevated, and hCG was demonstrated within syncytiotrophoblastic giant cells immunohistochemically. The clinical diagnosis was stage Ia dysgerminoma with syncytiotrophoblastic giant cells. Her karyotype was 46,XX and the sex-determining region Y gene was not detected in tumor DNA by polymerase chain reaction analysis. Conclusion: This rare Gonadal tumor may arise from dysgenetic gonads in addition to gonadoblastoma and Pure dysgerminoma. It is an example of tumorgenesis in Pure Gonadal Dysgenesis with no identifiable Y chromosome component.
