OBJECTIVETo investigate the phenotype-genotype association of isodicentromere Y chromosome by analysis of two female patients carrying the chromosome with sexual development disorders.

METHODSThe karyotypes of the two patients were determined by application of conventional G banding of peripheral blood samples and fluorescence in situ hybridization (FISH). PCR was applied to detect the presence of SRY gene.

RESULTSConventional karyotype analysis showed case 1 to be a mosaic: mos.45,X[38]/46,X,+mar[151]/47,XY,+mar[5]/47,X,+mar × 2[2]/46,XY[4], FISH showed that 12 different cell lines were presented in the karyotype of case 1 and partial cell lines with SRY gene, the marker is an isodicentromere Y chromosome [idic(Y)(p)]. No mutation was found in the SRY gene. The karyotype of case 2 was mos.45,X[25]/46,X,+mar[35]. FISH showed the marker to be an idic(Y)(p) without the SRY gene.

CONCLUSIONThe karyotype of patients carrying idic(Y)(p) seems unstable, and female patients have the characteristics of short stature and secondary sexual hypoplasia. Karyotype analysis combined with FISH analysis can accurately determine the breakpoint of idic(Y) and identify the types of complex mosaic, which may facilitate genetic counseling and prognosis.

Adolescent ; Child ; Chromosomes, Human, Y ; Disorders of Sex Development ; genetics ; Female ; Humans ; Karyotype ; Sex Chromosome Aberrations ; Sex-Determining Region Y Protein ; genetics

46, XX male is a rare sex cluomasomal constitution characterized by the development of bilateral testis in persons who lack a Y chomosome. The majority of affected persons have normal external genitalia and usually seek medical advice due to infertility, hypogonadism and/or gynecomastia in adulthood. Although Y chromosomsl sequences can be detected in the majority of male subjects with 46, XX karyotype, several studies have shown thst approximately 10 % of patients lack Y chromosomal material including the SRY ( sex-determining region of Y-chromosome) gene. Several hypothesis have been proposed to explain the etiology of this constitution. 1. Translocation of the testis-determining factor (TDF) fiom the Y to the X chromosome or autosome. 2. Acquisition of Y chromosome function by a mutant autosomal or X-linked gene. 3. Undetected mosaicism with Y-bearing cell line 4. Loss of Y chmmosome hom the XXY Klinefelter zygote. We experienced a case of 46, XX male who was 30 years old. We report a case with review of the literature.
Adult ; Cell Line ; Constitution and Bylaws ; Genes, X-Linked ; Genitalia ; Gynecomastia ; Humans ; Hypogonadism ; Infertility ; Karyotype ; Male* ; Mosaicism ; Sex-Determining Region Y Protein ; Testis ; X Chromosome ; Y Chromosome ; Zygote

In order to investigate the relationship between sex dysplasia and sex-determining region Y (SRY) gene, 8 patients with sexual abnormality were analyzed by cytogenetic and molecular genetic methods. Fluorescence in situ hybridization (FISH) using PY3.4, X alpha satellite, and SRY probes was performed in each case to analyze the sex chromosome translocation and gene translocation. SRY gene was amplified by polymerase chain reaction (PCR) and its mutation was detected by direct sequencing. The results showed that among 8 patients, 5 were positive for SRY and the remaining negative for SRY. In the patients positive for SRY genes, 3 presented testes and the left 2 streak ovaries. In the patients negative for SRY, only one case presented testes, while 2 ovaries. Direct sequencing demonstrated that all SRY genes were normal in the patients positive for SRY genes. FISH technique demonstrated that SRY genes translocated from Ypter to Xpter in 2 46,XX phenotypic males positive for SRY genes. It was concluded that SRY gene is strongly involved in male sex determination, while a sequence of other genes may be taken into account in sexual development.
Female ; Genes, sry ; genetics ; Gonadal Dysgenesis, 46,XX ; genetics ; Gonadal Dysgenesis, 46,XY ; genetics ; Humans ; Male ; Sex Chromosome Disorders ; genetics ; Sex-Determining Region Y Protein ; genetics

OBJECTIVETo investigate the value of direct sequencing of sex-determining region Y (SRY) gene, as well as peripheral blood karyotype analysis, in the diagnosis of disorders of sex development (DSD) among children and adolescents with ambiguous genitalia.

METHODSThe karyotypes of 20 children and adolescents with ambiguous genitalia were determined by conventional G-banding analysis. PCR amplification was used to detect SRY gene in these patients, and direct sequencing was used to judge whether there was SRY gene mutation.

RESULTSOf the 20 cases, 17 were positive for SRY gene, and 3 were negative for SRY gene. Direct sequencing revealed no SRY gene mutation in the positive cases, however karyotype analysis found 4 special karyotypes in these patients: 46, XY, del(Y) (q12)/45, X; 46, XY, add(Y) (p11); 46, XY, r(9); 46, XY, 9qh+.

CONCLUSIONSSRY gene detection can help determine the type of DSD among children and has the advantage of quick detection. Used together with G-banding analysis, it is helpful for primary diagnosis of DSD among children.

Adolescent ; Child ; Child, Preschool ; Chromosome Banding ; Disorders of Sex Development ; diagnosis ; genetics ; Humans ; Infant ; Infant, Newborn ; Karyotype ; Sex-Determining Region Y Protein ; genetics

In order to investigate the relationship between sex dysplasia and sex-determining region Y (SRY) gene, 8 patients with sexual abnormality were analyzed by cytogenetic and molecular genetic methods. Fluorescence in situ hybridization (FISH) using PY3.4, X alpha satellite, and SRY probes was performed in each case to analyze the sex chromosome translocation and gene translocation. SRY gene was amplified by polymerase chain reaction (PCR) and its mutation was detected by direct sequencing. The results showed that among 8 patients, 5 were positive for SRY and the remaining negative for SRY. In the patients positive for SRY genes, 3 presented testes and the left 2 streak ovaries. In the patients negative for SRY, only one case presented testes, while 2 ovaries. Direct sequencing demonstrated that all SRY genes were normal in the patients positive for SRY genes. FISH technique demonstrated that SRY genes translocated from Ypter to Xpter in 2 46,XX phenotypic males positive for SRY genes. It was concluded that SRY gene is strongly involved in male sex determination, while a sequence of other genes may be taken into account in sexual development.
Genes, sry/*genetics ; Gonadal Dysgenesis, 46,XX/genetics ; Gonadal Dysgenesis, 46,XY/genetics ; Sex Chromosome Disorders/*genetics ; Sex-Determining Region Y Protein/*genetics

ObjectiveTo identify the etiology of chromosome abnormality in an infertile man and analyze the correlation between the genotype and phenotype.

METHODSWe analyzed the karyotype of an infertile male using the routine G-banding technique and then the chromosome abnormality of the patient by Illumina Human CytoSNP-12 Beadchip array.

RESULTSNegative results were found in the examination of the sex-determining region Y (SRY) gene and the STR locus in the AZF zone of the patient. The karyotype of the patient was 46, XX. SNP array showed a 1.05 Mb 19p12 duplication and a 0.93 Mb Xq27.1 duplication.

CONCLUSIONSThe patient was confirmed as a case of 46,XX male syndrome. The increased copies of the FGF13 gene may be the major causes of abnormal sex determination and testis development.

46, XX Testicular Disorders of Sex Development ; diagnosis ; genetics ; Chromosome Aberrations ; Chromosome Banding ; Genetic Testing ; Humans ; Infertility, Male ; genetics ; Karyotype ; Karyotyping ; Male ; Phenotype ; Sex-Determining Region Y Protein ; genetics

OBJECTIVE: To explore the pathogenesis for a SRY-negative male with 46,XX disorder of sex development (DSD). METHODS: Peripheral blood samples of the patient and his family members were subjected to chromosomal karyotyping, routine PCR, real-time fluorescence quantitative PCR, whole exome sequencing and whole genome sequencing. The data was analyzed with NextGENe software. RESULTS: Both the proband and his brother presented a 46,XX karyotype with negative SRY gene, while their father presented normal phenotype and karyotype with positive SRY gene. No pathogenic variant associated with sex development was detected by whole exome sequencing, while a 243 kb duplication was detected by whole genome sequencing in the 5' upstream region of the SOX9 gene in the proband, his brother and father. The same duplication was not found in his sister and mother. CONCLUSION The 243 kb duplication at the 5' upstream of the SOX9 gene may predispose to the 46,XX DSD in this family. It is speculated that there exist an unknown core regulatory element in the upstream of the SOX9, and its duplication may trigger expression of SOX9 and initiate testicular differentiation in the absence of SRY gene.
Disorders of Sex Development/genetics* ; Female ; Humans ; Male ; Mutation/genetics* ; Regulatory Sequences, Nucleic Acid/genetics* ; Sex-Determining Region Y Protein/genetics* ; Testis ; Whole Exome Sequencing

OBJECTIVETo isolate fetal DNA from maternal plasma and examine its fetal origin.

METHODSFetal DNA in maternal plasma was isolated from 150 samples in the first trimester and mid-trimester of pregnancy, respectively. Real-time fluorescence quantitative polymerase chain reaction PCR (FQ-PCR) was used to determine sex-determining region Y (SRY) gene on Y chromosome.

RESULTSEighty-two women in the first trimester and 90 women in the mid-trimester carried male fetuses,70 and 90 samples of them were positive, respectively. The mean concentrations were (58.82+/-20.90) copies/ml and (152.08+/-62.61) copies/ml. The results of FQ-PCR were negative in the women who carried female fetuses.

CONCLUSIONThe results show that fetal SRY gene can be found at a time as early as 42 days of gestation in maternal plasma by the use of FQ-PCR. The number of fetal DNA increases with gestational age. The real-time FQ-PCR is of great value in the non-invasive prenatal diagnosis.

Adult ; DNA ; blood ; genetics ; isolation & purification ; Female ; Fetus ; metabolism ; Fluorescence ; Gestational Age ; Humans ; Polymerase Chain Reaction ; methods ; Pregnancy ; Pregnancy Trimesters ; Sex-Determining Region Y Protein ; genetics

OBJECTIVETo test the hypothesis that malignant tumor metastasis is mediated also through a non-cellular, essentially molecular, mechanism in addition to the cellular pathway.

METHODSThe sex-determining region on the Y chromosome was detected as the marker of the primary tumors using PCR in Lewis lung carcinoma (LLC) in vitro and in female C57BL/6 mice bearing LLC with spontaneous metastasis. The macroscopic and microscopic metastases in the tumor-bearing mice were examined for SRY expression by PCR and in situ hybridization, using the tissues from male and female mice as the positive or negative controls.

RESULTS AND CONCLUSIONPositive SRY gene expression was detected in the metastatic foci in the LLC-bearing female mice, suggesting the origination of these tumor cells from the primary tumor foci. We have failed to verify the non-cellular metastasis hypothesis in this animal experiment, but given the limitations of this experiment, we consider further investigation still necessary for verification of this hypothesis using other methods.

Animals ; Carcinoma, Lewis Lung ; genetics ; pathology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Transplantation ; Sex-Determining Region Y Protein ; genetics ; metabolism

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*