Adult ; Animals ; Female ; Frameshift Mutation/genetics* ; Genes, sry ; Gonadal Dysgenesis, 46,XY/genetics* ; Humans ; Menarche ; Ovary/pathology* ; Oviducts/pathology* ; Sex-Determining Region Y Protein/genetics*

OBJECTIVE: To explore the pathogenesis of a 46,XY female with sex reversal. METHODS: Peripheral blood lymphocytes of the patient were subjected to G-banding karyotype analysis. Sex chromosomes were analyzed with fluorescence in situ hybridization (FISH). SRY gene was analyzed by Sanger sequencing. The whole exome of the patient was subjected to next generation sequencing. Copy number variations (CNVs) of the NR0B1, SF1, SRY, SOX9 and WNT4 genes were validated by multiplex ligation-dependent probe amplification (MLPA). RESULTS: The patient had a 46,XY karyotype. FISH analysis showed that her sex chromosomes were X and Y. No mutation was found in the SRY gene, and no pathogenic mutation was detected in her exome. However, a duplication spanning approximately 67.31 kb encompassing the MAGEB1, MAGEB3, MAGEB4 and NR0B1 genes at Xp21, was predicted by software analysis. MLPA confirmed duplication of the NR0B1 gene in the patient and her mother. CONCLUSION A duplication fragment of Xp21 encompassing the NR0B1 gene in the 46,XY female with sex reversal is transmitted from her asymptomatic carrier mother. Attention should be paid towards the insidious nature and high morbidity of this duplication.
DAX-1 Orphan Nuclear Receptor ; genetics ; DNA Copy Number Variations ; Female ; Gene Duplication ; Genes, sry ; Gonadal Dysgenesis, 46,XY ; genetics ; Humans ; In Situ Hybridization, Fluorescence

Adult ; Azoospermia/genetics* ; Follicle Stimulating Hormone/metabolism* ; Gonadal Dysgenesis, Mixed/pathology* ; Growth Disorders/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Infertility, Male/genetics* ; Karyotype ; Luteinizing Hormone/metabolism* ; Male ; Mosaicism ; Testis/pathology* ; Testosterone/metabolism* ; Turner Syndrome

Testicular microlithiasis (TM) is one of the symptoms of testicular dysgenesis syndrome (TDS). TM is particularly interesting as an informative marker of testicular germ cell tumors (TGCTs). KIT ligand gene (KITLG), BCL2 antagonist/killer 1 (BAK1), and sprouty RTK signaling antagonist 4 (SPRY4) genes are associated with a high risk of TGCTs, whereas bone morphogenetic protein 7 gene (BMP7), transforming growth factor beta receptor 3 gene (TGFBR3), and homeobox D cluster genes (HOXD) are related to TDS. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated allele and genotype frequencies for KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), BAK1 (rs210138), BMP7 (rs388286), TGFBR3 (rs12082710), and HOXD (rs17198432) in 142 TGCT patients, 137 TM patients, and 153 fertile men (control group). We found significant differences in the KITLG GG_rs995030 genotype in TM (P = 0.01) and TGCT patients (P = 0.0005) compared with the control. We also revealed strong associations between KITLG_rs1508595 and TM (G allele, P = 0.003; GG genotype, P = 0.01) and between KITLG_rs1508595 and TGCTs (G allele, P = 0.0001; GG genotype, P = 0.0007). Moreover, there was a significant difference in BMP7_rs388286 between the TGCT group and the control (T allele, P = 0.00004; TT genotype, P = 0.00006) and between the TM group and the control (T allele, P = 0.04). HOXD also demonstrated a strong association with TGCTs (rs17198432 A allele, P = 0.0001; AA genotype, P = 0.001). Furthermore, significant differences were found between the TGCT group and the control in the BAK1_rs210138 G allele (P = 0.03) and the GG genotype (P = 0.01). KITLG and BMP7 genes, associated with the development of TGCTs, may also be related to TM. In summary, the KITLG GG_rs995030, GG_rs1508595, BMP7 TT_rs388286, HOXD AA_rs17198432, and BAK1 GG_rs210138 genotypes were associated with a high risk of TGCT development.
Adolescent ; Adult ; Calculi/genetics* ; Case-Control Studies ; Cohort Studies ; DNA/genetics* ; Gene Frequency ; Genetic Predisposition to Disease ; Gonadal Dysgenesis/genetics* ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal/genetics* ; Polymerase Chain Reaction ; Testicular Diseases/genetics* ; Testicular Neoplasms/genetics* ; Ultrasonography ; Young Adult

Objective: To explore the relationship between the clinical and genetic features of a short-statured azoospermia male with the karyotype of 45,X. METHODS: Using GTG-banded chromosome analysis, we performed karyotyping for a 150 cm-high infertile male with azoospermia and investigated the presence and location of the genes on the Y chromosome by FISH and PCR. RESULTS: GTG-banded chromosome analysis showed the karyotype of the patient to be 45,X,add(14)(p11). The results of PCR manifested the deletion of AZFa, AZFb, AZFc, and AZFd in the SRY gene. FISH revealed the translocation of the short arm of the Y chromosome to that of chromosome 14 and deletion of most proportions of its long arm, with the disruption site close to the centromere region. The karyotype of the patient was 45,X,der(Y)t(Y;14)(q11;q11.2), 14.ish (SRY+, CEP Y+ , DYZ1－). CONCLUSIONS The karyotype of the patient was unbalanced Y/14 translocation. The SRY gene is the key to maleness. The deletion of AZFa－ d induces spermatogenic disturbance, and the deletion of the q arm of the Y chromosome may be related with short stature.
Azoospermia ; genetics ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Y ; genetics ; Gonadal Dysgenesis ; genetics ; Humans ; Infertility, Male ; genetics ; Karyotyping ; methods ; Male ; Polymerase Chain Reaction ; SOXB1 Transcription Factors ; genetics ; Translocation, Genetic ; genetics

OBJECTIVETo investigate the clinical and genetic characteristics of a patient with mixed gonadal dysgenesis.

METHODSClinical data was collected. The patient was subjected for serum hormone testing and G-banding chromosomal analysis. Sex-determining region of Y-chromosome (SRY) gene and azoospermia factor (AZF) a, b, c regions were analyzed with multiple polymerase chain reaction (PCR) and whole gene sequencing.

RESULTSAll serum hormone testing were normal. The karyotype of the patient was 45,X/46,X,Yqh-. PCR has proven the presence of SRY, ZFY and AZFa, and deletion of AZFb and AZFc regions. No mutation was detected in the sequence of the SRY gene. Abdominal computerized tomography has detected a huge mass in the pelvic cavity, which was positive for PLAP and CD117 on immunohistochemistry stain.

CONCLUSIONBased on clinical data and result of genetic testing, the patient was diagnosed with mixed gonadal dysgenesis. Pathological and immunohistochemistry analysis of the transformed gland has confirmed the diagnosis of seminoma. For patient with a karyotype of 45,X/46,X,Yqh-, the risk of seminoma may be related with the presence of SRY gene.

Chromosome Banding ; Chromosomes, Human, Y ; genetics ; Female ; Genes, sry ; Gonadal Dysgenesis, Mixed ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Sex Determination Analysis

OBJECTIVETo explore the significance of karyotype analysis in screening sperm donors.

METHODSFrom January 1, 2004 to December 31, 2008, a total of 2537 potential sperm donors passed our preliminary screening, and all were routinely karyo-typed via peripheral blood. Follow-ups were conducted on the pregnancy outcome and congenital malformation after artificial insemination with the sperm from the qualified donors.

RESULTSAmong the 2537 qualified sperm donors, 2362 were of the normal karyotype 46, XY and 135 showed polymorphism. Abnormal karyotype was found in 6 cases, and controversial abnormal karyotype in 34.

CONCLUSIONKaryotype analysis can reduce the risk of chromosomal disease in neonates from artificial insemination, and genetic counseling for abnormal karyotype sperm donors may help them solve their future reproductive problems.

Adult ; Chromosome Aberrations ; Chromosome Disorders ; prevention & control ; Genetic Testing ; Gonadal Dysgenesis, 46,XY ; genetics ; prevention & control ; Humans ; Karyotyping ; Male ; Sperm Banks ; Tissue Donors ; Young Adult

OBJECTIVETo investigate the phenotype, pathogenesis and molecular biological features of 46, XX testicular disorder of sex development.

METHODSWe obtained the history of 2 patients with 46, XX testicular disorder of sex development, examined the cavitas pelvis by type-B ultrasonography, analyzed the karyotype of the chromosome, and detected the genes SRY, YRRM1, DYS240 and DAZ by PCR amplification.

RESULTSMicrorchidia, azoospermia and maldevelopment of secondary sex characteristics were observed in both of the patients, but ultrasonography revealed no female internal genitals. Their chromosome gender was karyotyped as 46, XX, with the SRY gene positive in both, but the YRRM1 gene positive in only one of the cases.

CONCLUSIONChromosome karyotyping and detection of the SRY gene for patients with abnormal sex development can give us an insight into the genetic pathogenesis and provide us with scientific evidence for the diagnosis and treatment of the condition.

Adult ; Genes, sry ; Gonadal Dysgenesis, 46,XX ; genetics ; Humans ; Male ; Nuclear Proteins ; genetics ; RNA-Binding Proteins ; genetics

Researches on the testicular dysgenesis syndrome (TDS) have flourished in the recent decade, and a widely accepted view on its pathogenesis is that environmental endocrine disrupting chemicals (EDCs) act on Leydig cells and/or testicular Sertoli cells, resulting in abnormal development of the testis and leading to the symptoms of TDS. Molecular biological studies suggest a correlation of TDS etiology with insulin-like factor 3 (INSL-3), androgen receptor (AR), P27kip, WT-1 and Müllerian inhibiting substance (MIS). This review focuses on the progress in current researches on the etiology and mechanism of TDS.
Cryptorchidism ; Gonadal Dysgenesis ; etiology ; genetics ; Humans ; Male ; Testicular Diseases ; etiology ; genetics ; Testicular Neoplasms

A 23-yr-old phenotypic female was seen for primary amenorrhea. Her pubic hair was relatively well developed and external genitalia showed normal female appearance, but breast development was retarded. Transvaginal ultrasonographic examination showed a small uterus with indistinct streak gonads, but both ovaries were not detected. Cytogenetic study revealed 46,XY. In FISH and PCR, the sex-determining region of Y chromosome (SRY) was not detected. We report here a case of 46,XY pure gonadal dysgenesis with loss of the SRY.
Adult ; Chromosomes, Human, Y ; Female ; *Gene Deletion ; *Genes, sry ; Gonadal Dysgenesis, 46,XY/*diagnosis/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Polymerase Chain Reaction