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

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

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 investigate the molecular mechanism of sex reversal in a 46,XY female patient.

METHODSClinical data was collected. Peripheral blood lymphocytes were cultured for G-banding chromosomal analysis and DNA extraction. Sex-determining region of Y-chromosome (SRY) gene was analyzed with polymerase chain reaction (PCR) and DNA sequencing .

RESULTSAlthough the patient has a female appearance, he has a karyotype of 46,XY. The SRY gene can be detected in all samples. The 6th base of SRY gene coding region was deleted, resulting in a frameshifting mutation and premature termination of protein translation.

CONCLUSIONThe sex reversal of the patient is probably due to abnormal embryonic development caused by the SRY gene mutation.

Adolescent ; Amino Acid Sequence ; Disorders of Sex Development ; genetics ; Female ; Genes, sry ; Humans ; Molecular Sequence Data

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

OBJECTIVETo investigate the relationship between the phenotypes in XX male patients and the sex determining region(SRY) gene.

METHODSMultiple polymerase chain reactions were carried out in 6 male patients with karyotype of 46, XX, and then the PCR products were sequenced directly.

RESULTSThree cases of male infertility were positive for the SRY gene without evident malformation in their extra genitalia, while 3 cases with testes were negative for the SRY gene, with evident malformation in their extra genitalia.

CONCLUSIONThe SRY gene is key in sex determination and development, yet there might be other important genes involved.

Adult ; Child, Preschool ; Genes, sry ; genetics ; Genitalia, Male ; pathology ; Humans ; Infant ; Male ; Phenotype ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sex Chromosome Aberrations ; Sex Chromosome Disorders ; genetics ; pathology

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

OBJECTIVETo establish a primed in situ labeling (PRINS) technique which can be more effective in detection of single copy gene.

METHODSOn the basis of traditional PRINS, new reagents and procedures, such as TaqStart antibody, four primers of the sex determining region Y (SRY) gene and TSA(TM) Biotin System were included in detection of the SRY gene. Meanwhile, fluorescence in situ hybridization(FISH) to detect the SRY gene was used as control.

RESULTSFifty metaphases were scored. PRINS labeling showed signals for the SRY on the Y chromosome at band Yp11.3 in all metaphases. These signals were as distinct as that from results of FISH.

CONCLUSIONThis improved method is ideal for rapidly localizing single copy genes and small DNA segments. And PRINS is a cost- and time-effective alternative to FISH.

Gene Dosage ; Genes, sry ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Metaphase ; genetics ; Primed In Situ Labeling ; methods

OBJECTIVETo analyze the clinical, molecular and cytogenetic features of 46, XX (SRY positive) male syndrome.

METHODSThe clinical features of 4 patients with 46, XX (SRY positive) male syndrome were analyzed retrospectively. Karyotyping, FISH, PCR amplification of the SRY gene, and Y-chromosome microdeletion were performed to study their molecular cytogenetic features.

RESULTSThe Four patients were all sociopsychologically males of short stature and came to hospital for infertility. Physical examination revealed that their testes were small in volume and soft in texture, but their penes were normal. Semen analyses showed complete azoospermia. Detection of serum sexual hormone suggested hypergonadotropic hypogonadism. All were karyotyped as 46, XX. Molecular analyses revealed the presence of the SRY gene and absence of AZFa, b and c of the Y chromosome. FISH analysis showed that SRY genes were translocated to Xp in 3 of the patients.

CONCLUSIONPhenotypically 46, XX (SRY positive) male patients are males generally, for the presence of the SRY gene in the whole genome and azoospermia due to the deletion of AZF. The clinical characteristics of the patient include testis dysgenesis, infertility and short stature. The long arm of the Y chromosome might contain the gene associated with body height. Extensive molecular and cytogenetic studies on 46, XX male syndrome may help to elucidate its genotype-phenotype relation.

Adult ; Body Height ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; Estradiol ; blood ; Follicle Stimulating Hormone ; blood ; Genes, sry ; Gonadal Dysgenesis, 46,XX ; blood ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Luteinizing Hormone ; blood ; Male ; Polymerase Chain Reaction ; Prolactin ; blood ; Syndrome