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.
Animals ; Humans ; Male ; Female ; Sertoli Cells/metabolism* ; Klinefelter Syndrome/genetics* ; Endothelial Cells ; Testis/metabolism* ; X Chromosome/metabolism* ; Mammals/genetics*

Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y (Sry), copy number of amelogenin, X-linked (Amelx), and inactive X specific transcripts (Xist) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.
Animals ; Azoospermia ; In Situ Hybridization, Fluorescence ; Karyotyping ; Klinefelter Syndrome/genetics* ; Mice ; Polymerase Chain Reaction

Female ; Fertilization in Vitro ; Humans ; Klinefelter Syndrome/genetics* ; Pregnancy ; Preimplantation Diagnosis ; Sperm Injections, Intracytoplasmic

Adult ; Fertilization in Vitro ; Humans ; Infertility, Male/therapy* ; Klinefelter Syndrome/genetics* ; Male ; Sperm Injections, Intracytoplasmic ; Sperm Retrieval

Klinefelter syndrome (KS) is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting (HRM) assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS, the ratios of ZFX/ZFY are altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts (5 ng-50 ng) and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity (100%) and specificity (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD per sample), easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.
DNA/genetics* ; Dried Blood Spot Testing ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Klinefelter Syndrome/diagnosis* ; Kruppel-Like Transcription Factors/genetics* ; Male ; Mass Screening/methods* ; Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVETo explore the genetic cause of a female case with intellectual development disorder.

METHODSG banding karyotyping was performed for the patient. Following DNA extraction, the coding sequence of SRY gene was amplified with PCR and subjected to Sanger sequencing. qPCR was used to detect the copy numbers of the SRY gene.

RESULTSThe karyotype of the patient was 47,XXY. PCR and qPCR analyses of the SRY gene showed a large deletion with null copy number.

CONCLUSIONThe female phenotype of the patient is probably due to deletion of the SRY gene on the Y chromosome. This is the first report of 47,XXY female case with deletion of the SRY gene in China.

Base Sequence ; Chromosome Banding ; Chromosomes, Human, Y ; genetics ; Female ; Genes, sry ; genetics ; Humans ; Intellectual Disability ; genetics ; Karyotype ; Karyotyping ; Klinefelter Syndrome ; genetics ; Male ; Polymerase Chain Reaction ; Review Literature as Topic ; Sequence Analysis, DNA ; methods ; Sequence Deletion ; Sequence Homology, Nucleic Acid

Klinefelter's syndrome (KS) is a most frequent sex chromosomal disorder in males, which is characterized by hypogonadism and infertility. The development of assisted reproductive technology has made it possible for KS males to father children. Microdissection testicular sperm extraction (mTESE) is widely considered to be the best method for sperm retrieval in KS patients. This article presents an overview on mTESE for men with non-mosaic KS in the aspects of its predictors, sperm retrieval rate, operation procedure, preoperative hormonal therapy, and postoperative complications and testosterone reduction.
Adult ; Humans ; Klinefelter Syndrome ; genetics ; Male ; Microdissection ; adverse effects ; methods ; Postoperative Complications ; etiology ; Sperm Retrieval ; Spermatozoa ; Testis ; Testosterone

No abstract available.
Adult ; Antineoplastic Agents/therapeutic use ; *Chromosome Deletion ; *Chromosomes, Human, Pair 9 ; Cytogenetic Analysis ; DNA Mutational Analysis ; Fusion Proteins, bcr-abl/*antagonists & inhibitors/genetics/metabolism ; Gene Expression Regulation ; Humans ; Incidental Findings ; Klinefelter Syndrome/complications/diagnosis/*genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications/diagnosis/*drug therapy/enzymology/genetics ; Male ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/*therapeutic use ; Remission Induction ; Time Factors ; Treatment Outcome

OBJECTIVETo analyze clinical characteristics of a combination of dystrophinopathies and Klinefelter's syndrome (karyotype 47, XXY) in one patient.

METHODThe patient was diagnosed as Duchenne muscular dystrophy (DMD) and Klinefelter's syndrome in Beijing Children's Hospital in March, 2013. The clinical manifestations, physical examinations and laboratory test results were analyzed respectively. The clinical characteristics of four cases reported previously were analyzed as well.

RESULTThe 8.5 years old boy presented with symptoms of walking disorder and developmental delay. The patient had facial dysmorphism, waddling gait, Gower's manoeuvre and enlarged calves.Serum creatine kinase level was 21 040 U/L, and he had mild intellectual impairment. Deletions of exons 49-54 of the dystrophin gene were found.Gene dosage analysis revealed a heterozygous deletion in his mother. Five cases have been reported till now, their age ranged from 3.5 to 18 years; 3 of them were DMD, while the other 2 cases were Becker muscular dystrophy (BMD). One of them, detected in pedigree study, whose weakness was minimal in contrast to the proband. The others came to the hospital because of walking disorder or developmental delay. All the patients had enlarged calves, some of them also had Gower's manoeuvre and waddling gait. The patients' height was between 3 rd and 50 th percentile, while 2 of them had facial dysmorphism.Some degree of mental impairment is usual. Their serum creatine kinase were 2 469-24 750 U/L.One of them was detected in pedigree study. Three of them were diagnosed by muscle biopsy, while in the other one mutation analysis was used.

CONCLUSIONThe combination of dystrophinopathies and Klinefelter's syndrome is quite rare, and has clinical features of these two diseases. Mutation analysis (or muscle biopsy) and karyotype analysis can finally diagnose the syndrome.

Child ; Creatine Kinase ; blood ; DNA Mutational Analysis ; Dystrophin ; genetics ; metabolism ; Exons ; genetics ; Gene Deletion ; Heterozygote ; Humans ; Intellectual Disability ; Klinefelter Syndrome ; complications ; diagnosis ; genetics ; Male ; Muscle Weakness ; etiology ; Muscular Dystrophy, Duchenne ; complications ; diagnosis ; genetics ; Mutation ; Pedigree

Acupuncture Therapy ; Humans ; Infant ; Klinefelter Syndrome ; genetics ; therapy ; Male