Molecular detection of a translocation (Y;15) in a 45,X male

Summary A 45,X male individual was shown to have a translocation of Y-chromosome material to the short arm or proximal long arm of chromosome 15. This translocation was detected by genomic DNA blotting and in situ hybridization with Y-chromosome-specific DNA probes.     

Azoospermia and cryptorchidism in a male with a de novo reciprocal t(Y;16) translocation

An apparently balanced reciprocal translocation between the long arm of the Y chromosome and the long arm of the chromosome 16 t(Y;16)(q12;q13) is described in an infertile man with azoospermia and cryptorchidism. The patient was phenotypically normal and had bilateral inguinal hernia repair with orchidopexy at the age of 8 years. Histological examination of testicular biopsies revealed maturation arrest. Y/autosome translocations in the literature are relatively rare and mostly associated with infertility. To our knowledge, this is the sixth report about the reciprocal t(Y;16) translocation in the literature but the first presenting with cryptorchidism.     

Mitotic and meiotic analysis of a reciprocal translocation t(Y;3) in an azoospermic male

Summary A balanced reciprocal translocation t(Y;3)(q11.2;q12) is detected in an azoospermic male, with a normal phenotype. Replication study shows no modification of the replication pattern of the bands of the rearranged chromosomes. Meiotic studies show a chain element at diakinesis. At the pachytene stage, the Y-body is in external contact with the sex vesicle. It is concluded that the integrity of the Y-chromosome is probably necessary for a normal meiotic process, and is more important than dosage effect due to complete or partial disomy of this chromosome.     

46,XX, der(15),t(Y;15)(q12;p11) karyotype in an azoospermic male

We report on a Yq/15p translocation in a 23-year-old infertile male referred for Klinefelter Syndrome testing, who had azoospermia and bilateral small testes. Hormonal studies revealed hypergonadotropic hypogonadism. Conventional cytogenetic procedures giemsa trypsin giemsa (GTG) and high resolution banding (HRB) and molecular cytogenetic techniques Fluorescence In Situ Hybridization (FISH) performed on high-resolution lymphocyte chromosomes revealed the karyotype 46,XX, t(Y;15)(q12;p11). SRY-gene was confirmed to be present by classical Polymerase Chain Reaction (PCR) methods. His father carried de novo derivative chromosome 15 [45,X, t(Y;15)(q12;p11)] and was fertile; the karyotype of the father using G-band technique confirmed a reciprocal balanced translocation between chromosome Y and 15. In the proband, the der (15) has been inherited from the father because the mother had a normal karyotype (46,XX). In the proband, the der (15) could have produced genetic imbalance leading to unbalanced robertson translocation between chromosome Y and 15, which might have resulted in azoospermia and infertility in the proband. The paternal translocation might have lead to formation of imbalanced ova, which might be resulted infertility in the proband. Sister''s karyotypes was normal (46,XX) while his brother was not analyzed.     

A t(Y;15) translocation with a deletion of the proximal Yq in a boy with mixed gonadal dysgenesis

Summary A Japanese boy with genital malformation and mixed gonadal dysgenesis is described. The karyotype appeared to be 46,X t(15;Y)(p13;q11). A comparison of the Q-positive segment on der(15) with that of the paternal Y chromosome revealed, however, the loss of over half of the Q-positive segment from the paternal Y during t(15;Y) translocation. The father had an unusually long Y chromosome that corresponded to a chromosome 18. DNA analysis further revealed a deletion of the non-fluorescent part of the long arm of the Y chromosome spanning interval 5–6.     

An azoospermic male with reciprocal translocation t(1;15)(q11;p11)

Summary The authors report on a case of 1;15 translocation and request contact with any colleagues who have observed similar cases.     

The segregation of a translocation t(1;4) in two male carriers heterozygous for the translocation

Summary We examined the meiotic segregation pattern of a t(1;4)(p36.2;q31.3) reciprocal translocation in two male cousins heterozygous for the translocation. The wife of subject 1 had four recognized spontaneous abortions and two carrier daughters, and the wife of subject 2 had three recognized spontaneous abortions and no liveborn children. The results showed that subject 1 had an imbalance rate of 54% and subject 2 had an imbalance rate of 61% with respect to the translocation. This was not statistically different (P = 0.3174) and the 95% confidence intervals overlapped for each segregation type. The sex ratio of X- and Y-bearing sperm was not statistically different than the expected 50%. The rate of structural abnormalities was 11.3% in subject 1 and 17.8% in subject 2. Both of these values were above the range of control subjects in our lab, but only subject 2's value fell outside the 95% confidence interval for the control population.     

A Y/15 translocation in a 45,X male with Prader-Willi syndrome

We report a male neonate with a 45 X karyotype; the long arm of a chromosome 15 was translocated onto the proximal long arm of the Y chromosome. Breakpoints were identified by in situ fluorescence hybridization (FISH) on the proximal 15q13 and Yq11.2. The derivative chromosome has no primary centromere. Clinical features were compatible with Prader-Willi syndrome. This is the first report case ofmonosomy 15q and Yq deletion with Prader-Willi syndrome.     

A family case of fertile human 45,X,psu dic(15;Y) males

We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family.     

Unbalanced translocation t(15;22) in "severe" Prader-Willi syndrome

A 13-year-old girl with an unbalanced karyotype 45,XX,-15,der(22)t(15;22)(q13;q13.3) de novo had Prader-Willi syndrome (PWS), (score 13.5), but with features of mental and physical retardation more severe than usually seen in PWS. The clinical diagnosis of PWS was confirmed by methylation analysis that showed absence of the paternal band. With GTG banding, the cytogenetic breakpoint on chromosome 15q13, with 15q14 intact, encompassed the PWS region, while the breakpoint on 22q was terminal. Investigations with FISH utilised ten different probes/combinations, namely SNRPN/PML, TUPLE1/22q13.3, TUPLE/ARSA, GABRB3, three YAC clones and one cosmid for specific regions within chromosome 15q, painting probes for the long arm of chromosomes 15 and 22 and a pantelomere probe. Deletion of SNRPN,TYAC 9 (at 15q11-12), TYAC19 (at 15q13) and GABRB3 (within the PWS locus), was evident on the derivative (22) chromosome, while TYAC10 (at 15q22), cos15-5 (at 15q22) and PML (15q22) were not deleted. On the der(22), 22q13.3 and ARSA were not deleted, but the most distal non specific pantelomeric probe was deleted. Thus, the severe phenotype could be attributable to deletion on chromosome 15q extending beyond q13 to q14, (further than the usual chromosome 15q deletion (q11-13) in PWS), or be related to loss of the very terminal 22q region (from ARSA to the pantelomere) or be due to genetic factors elsewhere in the genome.     

A 45,X male with evidence of a translocation of Y euchromatin onto chromosome 15

Summary A 19-year-old male with azoospermia was found to have a 45,X karyotype with additional euchromatic material on 15p. The parents' karyotypes are normal. The cytogenetic data, the positive H-Y-typing, and the presence of Yp-specific restriction fragments detected in the proband's genome by molecular DNA probes suggest that the short arm of the Y chromosome, including part of the centromere, is translocated onto the nucleolus organizer region (NOR) of chromosome 15.     

Molecular characterization of a Y;15 translocation segregating in a family

Summary We have used Y-specific and Y-derived DNA probes for in situ hybridization and Southern blotting analysis to characterize a Y;15 translocation showing normal Mendelian inheritance in a family. Cytogenetically there appeared to be an unbalanced translocation of Yqh to 15p; this translocation may be considered as a prototype of those translocations between Yq and the short arm of an acrocentric chromosome which have a population incidence of approximately 1 in 2,000. Our molecular studies showed that, in all probability, the breakpoints were near the border between Yq11.23 and Yq12, and in 15p11, respectively; the translocation is abbreviated t(Y;15)(q12;p11). Using the Y-specific probe pY431 in a quantitative Southern hybridization assay, normal females had no hybridization, female carriers and normal men had the same amount, and male carriers had twice that amount. Cytogenetic analysis and quantitative in situ hybridization using probes pY431 and pY3.4 were consistent with the hypothesis that the portion of Yq translocated to 15p comprised all of Yq12 and none of Yq11. The absence of Southern hybridization with probes specific for Yp and Yq11 confirmed this observation. Even though the family was ascertained through two brothers who both had schizophrenia and were carriers of the translocation, the clinical evaluation of a total of nine individuals with the translocation and five without it did not suggest its association with an abnormal phenotype.     

The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion.

Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found in dividing cells. Here we show that PML, a protein involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), is specifically bound to a NB. PML and several NB-associated proteins, found as auto-antigens in primary biliary cirrhosis (PBC), are co-localized and co-regulated. The APL-derived PML-RAR alpha fusion protein is shown to be predominantly localized in the cytoplasm, whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller nuclear clusters devoid of ultrastructural organization. RA administration (which in APL patients induces blast differentiation and consequently complete remissions) causes the re-aggregation of PML and PBC auto-antigens onto the NB, while PML-RAR alpha remains mainly cytoplasmic. Thus, PML-RAR alpha expression leads to a RA-reversible alteration of a nuclear domain. These results shed a new light on the pathogenesis of APL and provide a molecular link between NBs and oncogenesis.     

Aberrations of the synaptonemal complexes in a male 46,XY,-14,+der(14)t(Y;14)

An unbalanced translocation 46,XY,-14,+der(14)t(Y;14)(q11;p11) was observed in an azoospermic male, with reduced spermatogenesis and absent spermiogenesis. At the pachytene stage of spermatocyte 1, the segments of the 2 Y chromosomes, fluorescent with quinacrine mustard, were always found close together. This proximity was also demonstrated by the study of synaptonemal complexes, which showed, in addition, an unusual hypercondensation of the proximal segment of bivalent 14, adjacent to the translocated Y chromosome. This allows us to propose that this hypercondensation might correspond to an inactivation of the translocated autosome, which could be responsible of the degeneration of the germ cells.     

Translocation 46,X, t(Y;7)(q122;q11) in a case of male sterility]

A Y-autosome translocation--46,X,t(Y;7)(q122;q111)--in a steril man is reported and compared with others already reported in the literature.