1/23. A novel missense mutation in the HMG box region of the SRY gene in a Japanese patient with an XY sex reversal.The sex-determining region of the y chromosome, the SRY gene, located on the short arm of the y chromosome, is appreciated as one of the genes that is responsible for directing the process of sex differentiation. To date, 34 different mutations, including 29 missense and nonsense mutations in the SRY gene, have been described in XY female patients. We investigated the molecular basis of the sex reversal in one Japanese XY female patient by determining the nucleotide sequence of the SRY gene, using polymerase chain reaction and direct sequencing. We identified a novel mutation, of the substitution of Tyr for Asn at nucleotide position 87 (N87Y). This Asn residue is located within the dna-binding high-mobility-group (HMG) motif, which is considered to be the main functional domain of the SRY protein. Further, this amino acid, Asn, is a conserved residue among mammalian SRY genes. These findings indicate that this amino acid substitution may be responsible for the sex reversal in this patient.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
2/23. Penoscrotal hypospadias and coarctation of the aorta with mixed gonadal dysgenesis.A 45,X/46,Xidic(Y)(q11.2) mosaicism was found in a 4-year-old boy. The clinical appearance was characterized by bilateral cryptorchidism, penoscrotal hypospadias, short penis, and coarctation of the aorta. The latter is the only abnormality also seen in turner syndrome. A biopsy of the gonads revealed normal prepubertal testicular tissue. A chromosome analysis in all boys with penoscrotal, scrotal, or perineal hypospadias and a thorough examination of the heart in children with 45,X/46,XY mosaicism are recommended.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
3/23. Combination of hypospadias and maldescended testis as cardinal symptoms in gonosomal chromosome aberrations.Intersexual genitals or distinct hypospadias in combination with maldescended testis can be caused by endocrinological as well as chromosomal abnormalities. Even in early childhood such clinical findings require specific diagnostic procedures and subsequent treatment which is often invasive but has special importance as regards the early diagnosis of gonadal tumors. We present a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadias. Cytogenetic analyses revealed a mosaic karyotype 45, X/46, X, idic (Yp) with unequal distribution of the mosaic in different tissues. In consequence of this chromosomal aberration the patient had mixed gonadal dysgenesis which is associated with an increased risk of tumor development in the aberrant gonads. The principles of pediatric, urological, cytogenetic and endocrinological diagnostics and the mode of data collection in the presented case are described and discussed. Furthermore, a protocol for preventive screening is presented, which combines urological and endocrinological investigations in males with malformations of the genito-urinary tract to minimize the risk of tumor development in the aberrant gonads.- - - - - - - - - - ranking = 2keywords = chromosome (Clic here for more details about this article) |
4/23. Twenty-four hour, non-invasive, neonatal chromosome analysis--application in a case of mixed gonadal dysgenesis.INTRODUCTION: With the advent of interphase molecular fluorescent in-situ hybridisation (FISH), buccal mucosa can be used to provide an highly accurate assessment of those chromosomes most commonly causing abnormality in live-born children. CLINICAL PICTURE: A newborn child presented with ambiguous genitalia. The phallus-looking enlarged "clitoris" had a urethral opening at the ventral surface near the tip and the "labial" folds were completely fused. No definite gonads were palpable. Differential diagnostic possibilities included sex chromosome or a single gene abnormality such as congenital adrenal hyperplasia. Thus, one initial objective was to investigate the sex chromosomes. Buccal mucosa was used in conjunction with fluorescent molecular probes for the X and Y. This methodology enabled a firm diagnosis of a 45,X/46,XY mosiac to be made within 24 hours. Decisions could then be made concerning gender assignment. TREATMENT AND OUTCOME: Intervention by means of reconstructive surgery of the external genitalia would be made available at a later date. CONCLUSIONS: The use of buccal mucosa is non-invasive, easy to obtain and, when combined with molecular techniques, is reliable and accurate. The clinical implication of this methodology is that it will be especially useful in gender assignment or when rapid decisions on live-saving surgery have to be made in cases of possible aneuploidy.- - - - - - - - - - ranking = 3.5keywords = chromosome (Clic here for more details about this article) |
5/23. Cytogenetic and molecular characterization of two isodicentric Y chromosomes.We report the results of detailed molecular-cytogenetic studies of two isodicentric Y [idic(Y)] chromosomes identified in patients with complex mosaic karyotypes. We used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) to determine the structure and genetic content of the abnormal chromosomes. In the first patient, classical cytogenetics and FISH analysis with y chromosome-specific probes showed in peripheral blood lymphocytes a karyotype with 4 cell lines: 45,X[128]/46,X, idic(Y)(p11.32)[65]/47,XY, idic(Y)(p11.32)[2]/47,X, 2idic(Y)(p11. 32)[1]. No y chromosome material was found in the removed gonads. For precise characterization of the Yp breakpoint, FISH and fiberFISH analysis, using a telomeric probe and a panel of cosmid probes from the pseudoautosomal region PAR1, was performed. The results showed that the breakpoint maps approximately 1,000 Kb from Ypter. The second idic(Y) chromosome was found in a boy with mild mental retardation, craniofacial anomalies, and the karyotype in lymphocytes 47,X, idic(Y)(q11.23), i(Y)(p10)[77]/46,X, i(Y)(p10)[23]. To our knowledge, such an association has not been previously described. FISH and PCR analysis indicated the presence of at least two copies of the SRY gene in all analyzed cells. Using 17 PCR primers, the Yq breakpoint was shown to map between sY123 (DYS214) and sY121 (DYS212) loci in interval 5O in AZFb region. Possible mechanisms of formation of abnormal Y chromosomes and karyotype-phenotype correlations are discussed.- - - - - - - - - - ranking = 5keywords = chromosome (Clic here for more details about this article) |
6/23. Monozygotic twins with discordant sexual phenotypes due to different ratios of mosaicism of 47,X,idic(Y),idic(Y)/46,X, idic(Y)/45,X.We report monozygotic twins of different sexual phenotypes. One of the twins had complete female external genitalia except for a mild clitoromegaly. She had bilateral gonads consisting of the wavy stroma and scant dysgenetic seminiferous tubules. No androgen secretion was induced by gonadotrophin stimulation. The other twin had hypospadiac male genitalia. His gonads were located intrascrotally and he had good androgenic response to a stimulation test. Conventional and fluorescence in situ hybridization chromosome analysis disclosed that both twins had a 47,X,idic(Y),idic(Y)/46,X,idic(Y)/45,X and 47,X, mar x 2.ish idic(Y)(q11.2)(DYZ3 x 2)/46,X, mar.ish idic(Y)(q11.2)(DZY3 )/45,X. These twins were clinically monochorionic and allelotype analysis in these twins and their parents with microsatellite markers showed the affirmative probability of 0.999999994 for monozygosity. The ratio of mosaicism, gonadal histology, and testosterone productivity were reasonably correlated to the genital virilization in these monozygotic twins, showing discordant sexual phenotypes.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
7/23. True hermaphroditism with 46,X, 22p/46,XY and gonadal mosaicism detected by fluorescence in situ hybridization.A Japanese girl was diagnosed as true hermaphroditism with 46,X, mar/46,XY and the marker chromosome was determined on the short arm of chromosome 22 without alpha-satellite by fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) methods. At birth, she showed intersexual external genitalia, urethral-vaginal fistula and right inguinal hernia. The right gonad was revealed as an ovotestis, and the left was as an undifferentiated testis. The gonadal mosaicism was demonstrated directly in gonadal tissue by interphase FISH.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
8/23. Clinical management and molecular cytogenetic characterization in a 45,X/46,X,idic(Yp) patient with severe hypospadia.cryptorchidism and proximal hypospadia in a newborn are highly suspicious for an intersex disorder, and proper investigations should be planned immediately after birth. In some hypospadic patients, the presence of a palpable gonad in the scrotum may induce to assign the male sex, whereas the anatomy of internal and external genitalia could be extremely complex, requiring an accurate evaluation before any definitive attribution of gender. The authors present a case of an infant, referred to the hospital for surgical treatment of a proximal hypospadia, who showed ambiguous external genitalia, absence of the right gonad, a partially dysgenetic left testis, and presence of both mullerian and wolffian structures. cytogenetic analysis detected a mosaicism with a cell line showing an isodicentric Yp chromosome and a second one, a 45, X chromosomal complement. Because the baby had been assigned previously to male gender, he underwent a staged masculinizing correction of the genital anomalies. The authors discuss the necessity of a careful evaluation of these patients at birth by a multispecialistic team, for appropriate sex assignment and for the assessment of the risk of neoplastic degeneration.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
9/23. Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants.gonadoblastoma is an unusual mixed germ cell-sex cord-stromal tumor that has the potential for malignant transformation and 30% of all patients with gonadoblastoma develop germ cell tumors mainly dysgerminoma/seminoma. An additional 10% gives rise to other malignant germ cell neoplasms. This tumor affects a subset of patients with intersex disorders. The age at diagnosis is variable ranging from birth to the fourth decade, but around 94% of cases are diagnosed during the first three decades of life and there are few cases with gonadoblastoma diagnosed in infants. In this paper, we present the histological and molecular findings of four patients with gonadal dysgenesis who developed gonadoblastoma in the first 2 years of life and one case with bilateral dysgerminoma diagnosed at 15 years of age. The sex chromosomes of mosaic patients do not distribute homogenously in dysgenetic gonads; however, statistical analysis of FISH results revealed significant differences between the XY cell line in the gonadoblastoma compared with the dysgenetic testis. Our cases demonstrate that tumors could be present at a very early age, so the prophylactic removal of the gonads is advised.- - - - - - - - - - ranking = 2.5keywords = chromosome (Clic here for more details about this article) |
10/23. Unusual mixed gonadal dysgenesis associated with Mullerian duct persistence, polygonadia, and a 45,X/46,X,idic(Y)(p) karyotype.Mixed gonadal dysgenesis (MGD) is a developmental anomaly in which most of the patients have a dysgenetic testis, a contralateral streak and a 45,X/46,XY karyotype. This entity involves an heterogeneous group of gonadal and phenotypic abnormalities with a wide clinical spectrum. The phenotype depends on the ratio of testicular tissue which induces virilization. Although the karyotype in these patients is 45,X/46,XY, no genotype-phenotype correlation has been found to date. mullerian ducts persistence (MDP) in MGD is rare; however, four patients with both entities and different karyotypes have been described. Here we present the data on a newborn patient with an atypical MGD associated with MDP, two left testes, a gonadal streak on the right, and absence of Wolffian derivatives. PCR analysis identified all the Y-derived sequence tested in the father, while the patient had them all except the AZF b,c regions which were lost. FISH analysis of the paternal y chromosome documented Yq paracentric inversion while the patient's karyotype was 45,X/46,X,idic(Yp). No mutations were observed in MIS/MISRII genes.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
| | Next -> |