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World Literature
World Literature
as carrying 45,X karyotypes. At the time of this report, the ages of the prenatally identified mosaic patients ranged from 3 months to 10 years. The clinical features of the prenatally identified individuals were compared to 188 patients with 45,X karyotype and 41 45,X/46,XX mosaic patients. The prenatally identified mosaic patients have shown normal linear growth. Gonadotropin levels, measured between birth and 3 years of age in seven of the prenatally identified mosaic patients, were elevated in only one patient. Cardiac and renal anomalies were less common in the prenatally identified mosaic patients. In general, the postnatally identified mosaic patients had phenotypic features of Turner syndrome which brought them to medical attention, whereas the prenatally identified mosaic patients tended to have fewer characteristic features. In contrast, the prenatally identified 45,X individuals were not significantly different from the postnatally identified 45,X individuals. Most (55%) had been ascertained through abnormal prenatal ultrasound findings. The authors suggest that although the fortuitous detection of a 45,X/46,XX individual is generally associated with a milder phenotype, it is impossible to guarantee a normal outcome. Comment: This report of a milder phenotype in 45,XI 46,XX mosaics ascertained through prenatal amniocentesis performed for maternal reasons is similar to the report of a milder phenotype in 45,X/46,XX individuals reported by Chang et al. (The phenotype of 45,X/46,XX mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet 1990; 46: 156). Postnatally diagnosed mosaic individuals have an abnormal phenotype for which further evaluation has been sought. In contrast, the authors report that only 1 of the 12 prenatally diagnosed 45,X/46,XX individuals had a phenotype sufficiently abnormal to prompt further evaluation and karyotype analysis. The message from these reports is that a nurnber of individuals with sex chromosome mosaicism may be undiagnosed. However, the significance, if any, of unrecognized sex chromosome mosaicism remains to be determined.
39
Hsu SY, Kubo M, Chyn SY, et al: Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in expression during follicle development and repression of inhibin-o gene promoter. Mol Endocrinol 1995; 9:1356-1366.
Abnormalities in the WT1 gene have been described in the Denys-Drash syndrome which is associated with genital ambiguity and streak gonads. The protein product of the WT1 gene appears to be a transcription factor, and expression of its mRN A is limited to the kidney, uterus, and gonads. Abnormal gonadal development was observed in WT1-deficient transgenic mice. The authors of this study postulate that WT 1 may function as a repressor of ovarian differentiation genes. Expression of WT1 mRNA was investigated in rat ovaries during follicular development. Levels of ovarian WT1 mRNA were unaffected by estrogen or gonadotropin treatments and were highest on day 6, with subsequent decline during prepubertal development. Using in situ hybridization, WT1 mRNA expression was shown to be limited to the granulosa cells of primordial, primary, and secondary follicles. No WT1 signals were observed in follicles that had developed antrum. Cotransfection studies were performed to assess whether WT1 influences the promoter of the inhibin-n gene. As the amount of WT1 expression was increased, a dose-dependent decrease in inhibin-n promoter activity as measured by a luciferase reporter gene system was observed. The authors suggest that WT1 may play an important role in folliculogenesis through regulation of follicular arrest. Comment: The authors have performed studies showing the time course of WT 1 expression in relationship to the developing ovary in the rat. How is WT 1 regulated? The authors have shown that WT1 has the potential to repress inhibin-n gene expression. But, what is the interaction in vivo between these genes and their protein products? Further studies are necessary to determine the precise role of WT 1 in follicular development.
as carrying 45,X karyotypes. At the time of this report, the ages of the prenatally identified mosaic patients ranged from 3 months to 10 years. The clinical features of the prenatally identified individuals were compared to 188 patients with 45,X karyotype and 41 45,X/46,XX mosaic patients. The prenatally identified mosaic patients have shown normal linear growth. Gonadotropin levels, measured between birth and 3 years of age in seven of the prenatally identified mosaic patients, were elevated in only one patient. Cardiac and renal anomalies were less common in the prenatally identified mosaic patients. In general, the postnatally identified mosaic patients had phenotypic features of Turner syndrome which brought them to medical attention, whereas the prenatally identified mosaic patients tended to have fewer characteristic features. In contrast, the prenatally identified 45,X individuals were not significantly different from the postnatally identified 45,X individuals. Most (55%) had been ascertained through abnormal prenatal ultrasound findings. The authors suggest that although the fortuitous detection of a 45,X/46,XX individual is generally associated with a milder phenotype, it is impossible to guarantee a normal outcome. Comment: This report of a milder phenotype in 45,XI 46,XX mosaics ascertained through prenatal amniocentesis performed for maternal reasons is similar to the report of a milder phenotype in 45,X/46,XX individuals reported by Chang et al. (The phenotype of 45,X/46,XX mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet 1990; 46: 156). Postnatally diagnosed mosaic individuals have an abnormal phenotype for which further evaluation has been sought. In contrast, the authors report that only 1 of the 12 prenatally diagnosed 45,X/46,XX individuals had a phenotype sufficiently abnormal to prompt further evaluation and karyotype analysis. The message from these reports is that a nurnber of individuals with sex chromosome mosaicism may be undiagnosed. However, the significance, if any, of unrecognized sex chromosome mosaicism remains to be determined.
39
Hsu SY, Kubo M, Chyn SY, et al: Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in expression during follicle development and repression of inhibin-o gene promoter. Mol Endocrinol 1995; 9:1356-1366.
Abnormalities in the WT1 gene have been described in the Denys-Drash syndrome which is associated with genital ambiguity and streak gonads. The protein product of the WT1 gene appears to be a transcription factor, and expression of its mRN A is limited to the kidney, uterus, and gonads. Abnormal gonadal development was observed in WT1-deficient transgenic mice. The authors of this study postulate that WT 1 may function as a repressor of ovarian differentiation genes. Expression of WT1 mRNA was investigated in rat ovaries during follicular development. Levels of ovarian WT1 mRNA were unaffected by estrogen or gonadotropin treatments and were highest on day 6, with subsequent decline during prepubertal development. Using in situ hybridization, WT1 mRNA expression was shown to be limited to the granulosa cells of primordial, primary, and secondary follicles. No WT1 signals were observed in follicles that had developed antrum. Cotransfection studies were performed to assess whether WT1 influences the promoter of the inhibin-n gene. As the amount of WT1 expression was increased, a dose-dependent decrease in inhibin-n promoter activity as measured by a luciferase reporter gene system was observed. The authors suggest that WT1 may play an important role in folliculogenesis through regulation of follicular arrest. Comment: The authors have performed studies showing the time course of WT 1 expression in relationship to the developing ovary in the rat. How is WT 1 regulated? The authors have shown that WT1 has the potential to repress inhibin-n gene expression. But, what is the interaction in vivo between these genes and their protein products? Further studies are necessary to determine the precise role of WT 1 in follicular development.