Aim： To evaluate the occurrence of classical azoospermia factor （AZF） deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome （KS）. Methods： Blood samples were co...Aim： To evaluate the occurrence of classical azoospermia factor （AZF） deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome （KS）. Methods： Blood samples were collected from 95 azoospermic subjects with KS （91 subjects had a 47,XXY karyotype and four subjects had a mosaic 47,XXY/46, XY karyotype） and a control group of 93 fertile men. The values of testosterone, follicle stimulating hormone （FSH） and luteinizing hormone （LH） were measured. To determine the presence of Y chromosome microdeletions, polymerase chain reaction （PCR） of five sequence-tagged site primers （sY84, sY 129, sY 134, sY254, sY255） spanning the AZF region, was performed on isolated genomic DNA. Results： Y chromosome microdeletions were not found in any of the 95 azoosperrnic subjects with KS. In addition, using similar conditions of PCR, no microdeletions were observed in the 93 fertile men evaluated. The level of FSH in KS subjects was higher than that in fertile men （38.2 ± 10.3 mIU/mL vs. 5.4 ±2.9 mIU/mL, P 〈 0.001） and the testosterone level was lower than that in the control group （1.7 ±0.3 ng/mL vs. 4.3 ± 1.3 ng/mL, P 〈 0.001）. Conclusion： Our data and review of the published literature suggest that classical AZF deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KS subjects with a 47,XXY karyotype. In addition, routine screening for the classical AZF deletions might not be required for these subjects. Further studies including partial AZFc deletions （e.g. gr/gr or b2/b3） are necessary to establish other mechanism underlying severe spermatogenesis impairment in KS.展开更多
Aim： To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter＇s syndrome （KFS）. Methods： Blood and semen samples were collected from azoospermic patients with KFS （n = 14）...Aim： To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter＇s syndrome （KFS）. Methods： Blood and semen samples were collected from azoospermic patients with KFS （n = 14） and a control group of men of proven fertility （n = 13）. Semen analysis was done according to World Health Organization （WHO） guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization （FISH） and measurement of plasma follicle stimulating hormone （FSH） by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction （PCR） of 16 sequence tagged sites （STS） and three genes （DFFRY, XKRY and RBM1 Y） was performed on isolated genomic DNA. Testicular fine needle aspiration cytology （FNAC） was done in selected cases. Results： Y chromosome microdeletions spanning the azoospermia factor （AZF）a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion： Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques. （Asian JAndrol 2006 Jan; 8： 81-88）展开更多
Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular ...Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals.Among the different somatic cells,Sertoli cells showed the greatest transcriptome changes in KS patients.Further analysis showed that X-inactive-specific transcript(XIST),a key factor that inactivates one X chromosome in female mammals,was widely expressed in each testicular somatic cell type but not in Sertoli cells.The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes,and further disrupts their transcription pattern and cellular function.This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells.These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia.Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.展开更多
Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA resul...Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon.We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6%(59 out of 434). This gave a detection rate of 14.7%for developmental delay/intellectual disability(DD/ID,38/259) and 12% for autism spectrum disorders(ASDs,21/175). Thirty-three recurrent(n≥2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes(such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes).The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results(94.9%) had benefits, allowing earlier diagnosis(36/59), prioritized full clinical management(28/59), medication changes(7/59), a changed prognosis(30/59), and prenatal genetic counseling(15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential.We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.展开更多
文摘Aim： To evaluate the occurrence of classical azoospermia factor （AZF） deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome （KS）. Methods： Blood samples were collected from 95 azoospermic subjects with KS （91 subjects had a 47,XXY karyotype and four subjects had a mosaic 47,XXY/46, XY karyotype） and a control group of 93 fertile men. The values of testosterone, follicle stimulating hormone （FSH） and luteinizing hormone （LH） were measured. To determine the presence of Y chromosome microdeletions, polymerase chain reaction （PCR） of five sequence-tagged site primers （sY84, sY 129, sY 134, sY254, sY255） spanning the AZF region, was performed on isolated genomic DNA. Results： Y chromosome microdeletions were not found in any of the 95 azoosperrnic subjects with KS. In addition, using similar conditions of PCR, no microdeletions were observed in the 93 fertile men evaluated. The level of FSH in KS subjects was higher than that in fertile men （38.2 ± 10.3 mIU/mL vs. 5.4 ±2.9 mIU/mL, P 〈 0.001） and the testosterone level was lower than that in the control group （1.7 ±0.3 ng/mL vs. 4.3 ± 1.3 ng/mL, P 〈 0.001）. Conclusion： Our data and review of the published literature suggest that classical AZF deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KS subjects with a 47,XXY karyotype. In addition, routine screening for the classical AZF deletions might not be required for these subjects. Further studies including partial AZFc deletions （e.g. gr/gr or b2/b3） are necessary to establish other mechanism underlying severe spermatogenesis impairment in KS.
文摘Aim： To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter＇s syndrome （KFS）. Methods： Blood and semen samples were collected from azoospermic patients with KFS （n = 14） and a control group of men of proven fertility （n = 13）. Semen analysis was done according to World Health Organization （WHO） guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization （FISH） and measurement of plasma follicle stimulating hormone （FSH） by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction （PCR） of 16 sequence tagged sites （STS） and three genes （DFFRY, XKRY and RBM1 Y） was performed on isolated genomic DNA. Testicular fine needle aspiration cytology （FNAC） was done in selected cases. Results： Y chromosome microdeletions spanning the azoospermia factor （AZF）a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion： Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques. （Asian JAndrol 2006 Jan; 8： 81-88）
基金This work was supported by grants from the National Key R&D Program of China(2022YFC2702700)National Natural Science Foundation of China(82201756 and 82171597)+1 种基金China Postdoctoral Science Foundation(2021M703747)GuangDong Basic and Applied Basic Research Foundation(2021A1515111109)。
文摘Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals.Among the different somatic cells,Sertoli cells showed the greatest transcriptome changes in KS patients.Further analysis showed that X-inactive-specific transcript(XIST),a key factor that inactivates one X chromosome in female mammals,was widely expressed in each testicular somatic cell type but not in Sertoli cells.The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes,and further disrupts their transcription pattern and cellular function.This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells.These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia.Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
基金supported by grants from the National Natural Science Foundation of China (81761128035 and 81781220701)the Shanghai Municipal Science and Technology Committee (17XD1403200 and 18dz2313505)+2 种基金the Research Physician Project of Shanghai Municipal Education Commission (20152234)the Shanghai Municipal Health and Family Planning Commission (GDEK201709, 2017ZZ02026, and 2017EKHWYX02)the Scientific Program of Shanghai Shenkang Hospital Development Center (16CR2025B) of China
文摘Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon.We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6%(59 out of 434). This gave a detection rate of 14.7%for developmental delay/intellectual disability(DD/ID,38/259) and 12% for autism spectrum disorders(ASDs,21/175). Thirty-three recurrent(n≥2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes(such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes).The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results(94.9%) had benefits, allowing earlier diagnosis(36/59), prioritized full clinical management(28/59), medication changes(7/59), a changed prognosis(30/59), and prenatal genetic counseling(15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential.We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.
