Chondrodysplasia punctata with X;Y translocation

Summary We have studied a family in which the mother and her son were carriers of an X;Y translocation, der(X)t(X;Y) (p22.3;q11). The mother was of slightly short stature and had mildly short upper extremities. The son had epiphyseal punctate calcifications, mildly short extremities, a flattened nasal bridge, and mental retardation (chondrodysplasia punctata). The extra bands on the short arm of the X chromosome were identified as deriving from the long arm of the Y chromosome, using in situ hybridization with a Y-chromosome-specific DNA probe (pHY10). The chondrodysplasia punctata seen in our case may be associated with the abnormality of the distal short arm of the X chromosome caused by X;Y translocation.     

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.     

Y-to-X chromosome translocation observed in two generations

Summary A family is reported in which the mother and two sons are carriers of a Y-X translocation. The distal segment of the short arm of the X chromosome appears to have been deleted to give place to a translocation of the distal part of the long arm of the Y chromosome. Apart from short stature the mother is essentially free of stigmata, while the sons show a combination of mental retardation, hypertelorism, simian creases, clinodactyly, scanty palmar lines, and dry fragile skin. The cases described are discussed against the background of the few known previously published cases.     

Regional mapping of the human No. 1 and X chromosome in interspecific cell hybrids using an X/1 translocation.

Fibroblasts from a carrier of an X/1 translocation, 46,XY,t(X;1)(q28;q31), were fused with Chinese hamster cells. The resulting hybrids were analyzed for human No. 1 and X-chromosome markers. The data indicate that the loci for PGM1, PGD, PPH, and GuK1 are situated either in the long arm proximal to a break point in band 1q31 or in the short arm. The loci for Pep-C, FH, and GuK1 are located distal to the break point. HPRT and G6PD are probably situated distal to a break point in band q28 of the X chromosome; alpha-Gal A is situated proximal to the break point, either on the long or short arm of the chromosome.     

Synaptonemal complex of the sex-autosome trivalent in a male Indian muntjac

Bright-field microscopy of silver-stained pachytene spermatocytes of a male Indian muntjac, Muntiacus muntjak revealed that (a) the synapsis between the autosomal homologs, including the long arm of the X and Y₂, was normal, (b) the nucleolus organizer regions were present in both the No. 1 bivalent and the long arm of the X and Y₂, (c) the accessory structures of the X chromosome short arm in the forms of light and dark thickenings and the hairpin-like bend were present despite the X-autosome translocation, (d) a short synaptonemal complex was present between the Y₁ (real Y) and the short arm of the X chromosome, and (e) the centromeric orientation of the Y₁ and Y₂ chromosomes was in Cis configuration as opposed to the X chromosome.     

A possible exception to the critical region hypothesis.

Cytogenetic studies were done on a 5-year-old female with multiple congenital anomalies and mental retardation, revealing an unbalanced X/11 translocation. Her mother and phenotypically normal sister carry the balanced form of the translocation, while her brother has a normal 46,XY karyotype. Banding studies showed the breakpoints to be Xq22 and 11q13. These are remarkable for the following reasons: (1) the X breakpoint is within the critical region of the X chromosome, yet the balanced carrier does not manifest gonadal dysgenesis; and (2) the proband was trisomic for most of the long arm of chromosome 11. Late-replication studies of cells from the two balanced carriers showed inactivation of the normal X.     

De novo (11;13) translocation.

A male infant is described with unusual facial appearance, clubfeet, and moderate hydrocephalus internus without obvious deficiency in mental and physical development. Cytogenetic studies revealed a karyotype of 45,XY,--C,--D,+t(C;D). A chromosome 11 and a 13 are involved in the formation of the translocation chromosome. The long arm of chromosome 13 is linearly attached to the end of the long arm of chromosome 11 (tandem translocation). Chromosome material of the distal part of the long arm of chromosome 11, as well as the short arm plus the centromere of chromosome 13 seem to have been lost.     

Reciprocal translocation between Y chromosome long arm euchromatin and the short arm of chromosome 1

A case with an apparently balanced reciprocal translocation between the long arm of the Y chromosome and the short arm of chromosome 1 t(Y;1)(q11.2;p34.3) is described. The translocation was found in a phenotypically normal male ascertained by infertility and presenting for intra-cytoplasmatic sperm injection treatment. Histological examination of testicular biopsies revealed spermatogenic failure. Chromosome painting with probes for chromosome 1 and for the euchromatic part of the Y chromsome confirmed the translocation of euchromatic Y chromosomal material onto the short arm of chromosome 1 and of a substantial part of the short arm of chromosome 1 onto the Y chromosome. Among the Y/autosome translocations, the rearrangements involving long arm euchromatin of the Y chromosome are relatively rare and mostly associated with infertility. Microdeletion screening at the azoospermia locus revealed no deletions, suggesting another mechanism causing infertility in this translocation carrier.     

The nature of the 1;29 translocation in cattle as revealed by synaptonemal complex analysis using electron microscopy

Synaptonemal complex analyses were carried out by electron microscopy on surface-spread spermatocytes of one normal bull and two bulls that were heterozygous for the so-called 1;29 translocation. The autosomal bivalents of the normal karyotype, which could be arranged by size in a series, demonstrated kinetochores at the terminally located attachment plaques. One autosomal bivalent was clearly larger than the rest and apparently consisted of the long arm of the 1;29 translocation. The 1;29 translocation was the longest autosome in the set and had a kinetochore in a subtelocentric position. Some of the autosome pairs had nucleolus organizer regions in telomeric regions. The X and Y chromosomes, which were not paired at zygotene, demonstrated association in a very short segment at early pachytene; in no cells could a synaptonemal complex be seen between the X and Y. Very often the sex chromosomes were dissociated. At zygotene, a few, usually large, bivalents were unpaired proximally. This always also involved the proximal parts of the arms of the 1;29 translocation and their normal homologs. At early pachytene, the 1;29 trivalent, although to a less extensive degree, was also unpaired in the pericentric region. Configurations in which one chromosome, either 1 or 29, was completely paired with its corresponding arm in the 1;29 translocation chromosome also occurred. When unpaired proximally, the size of chromosome 1 agreed fairly well with the size of its corresponding arm, but the size of chromosome 29 was considerably larger than the corresponding arm of the 1;29 translocation chromosome. During late zygotene and early pachytene, the percent difference between chromosome 29 and its corresponding arm decreased, and at mid and late pachytene there had been a complete synaptic adjustment. The size difference and pairing behavior indicated that a deletion of the kinetochore and the most proximal segment of chromosome 29 had preceded the fusion with chromosome 1 into the 1;29 translocation. The unique structural appearance of the 1;29 translocation chromosome compared to that of other centric fusion translocations in cattle lends support to the theory of a monophyletic origin of the 1;29 translocation. The importance of the pairing behavior observed in governing recombination and chromosome disjunction is briefly discussed.     

Partial trisomy 13 as a result of de novo (6p;13q) translocation

Summary A newborn infant with the clinical features of the Patau syndrome was found to have excess chromosome 13 material present as a tandem translocation involving the short arm of chromosome 6 and the long arm of an extra chromosome 13: 46,XY,t(6;13)(p24;q12). The major part of the long arm of the extra chromosome 13 was attached linearly (tandem translocation) to the short arm of chromosome 6. Both parents were phenotypically and karyotypically normal.     

Assignment of Three Gene Loci (Pgk, Hgprt, G6pd) to the Long Arm of the Human X Chromosome by Somatic Cell Genetics

The intrachromosomal localization of three X-linked gene loci (PGK, HGPRT and G6PD) has been determined using a somatic cell genetic approach. A human cell line possessing an X/14 translocation was used as one parent in the formation of human/mouse hybrids. The translocation separates the human X into two parts: Xp and t(Xq14q). The data indicate that all three X-linked loci segregate with the t(Xq14q) rearrangement product thus permitting their assignment to the X chromosome's long arm. Secondary rearrangements and data from other laboratories suggest that the order of the the three markers from the centromere to the distal end of the X long arm is PGK, HGPRT, G6PD. It was also observed that NP, an autosomal locus, segregated with the t(Xq14q) chromosome. This provides strong support for the assignment of NP to 14.     

Mapping of the Menkes locus to Xq13.3 distal to the X-inactivation center by an intrachromosomal insertion of the segment Xq13.3-q21.2

Summary During a systematic chromosomal survey of 167 unrelated boys with the X-linked recessive Menkes disease (MIM 309400), a unique rearrangement of the X chromosome was detected, involving an insertion of the long arm segment Xq13.3-q21.2 into the short arm at band Xp11.4, giving the karyotype 46,XY,ins(X) (p11.4q13.3q21.2). The same rearranged X chromosome was present de novo in the subject's phenotypically normal mother, where it was preferentially inactivated. The restriction fragment length polymorphism and methylation patterns at DXS255 indicated that the rearrangement originated from the maternal grandfather. Together with a previously described X;autosomal translocation in a female Menkes patient, the present finding supports the localization of the Menkes locus (MNK) to Xq13, with a suggested fine mapping to sub-band Xq13.3. This localization is compatible with linkage data in both man and mouse. The chromosomal bend associated with the X-inactivation center (XIC) was present on the proximal long arm of the rearranged X chromosome, in line with a location of XIC proximal to MNK. Combined data suggest the following order: Xcen-XIST(XIC), DXS128-DXS171, DXS56-MNK-PGK1-Xqter.     

The X-autosome translocation in the common shrew (Sorex araneus L.): late replication in female somatic cells and pairing in male meiosis

Common shrews have an XX/XY₁Y₂ sex chromosome system, with the X chromosome being a translocation (tandem fusion) between the original X and an autosome; in males this autosome is represented by the Y₂ chromosome. From G-banded chromosomes, the Y₂ is homologous to the long arm and centromeric part of the short arm of the X. The region of the X that is homologous to the Y₂ and also the telomeric region of the short arm of the X were found to be early replicating in somatic cells from a female shrew after 5-bromo-2-deoxyuridine (BrdU) treatment in vitro. The remainder of the short arm of the X was shown to be late replicating. Electron microscopic examination of synaptonemal complexes in males at pachytene revealed pairing of the Y₂ axis with the long arm of the X, and Y₁ with the short arm. At early stages of pachytene, there is apparently extensive nonhomologous pairing between the X and Y₁. In essence, the short arm of the shrew X chromosome behaves like a typical eutherian X chromosome (it is inactivated in female somatic cells and is paried with the Y₁ during male meiosis) while the long arm behaves like an autosome (escapes the inactivation and pairs with the Y₂).     

Exclusion of the HLA locus from a large portion of the long arm of chromosome 6.

HLA antigens were determined in two infants with multiple congenital anomalies and in their healthy parents and one sibling. One infant had a deletion of a major portion of the long arm of chromosome 6. The other child had a translocation of a similar piece of chromosome 6 to the short arm of chromosome 3. The mother and the maternal grandmother showed this translocation in a balanced state. The HLA types of both children and their parents exclude the localization of the major histocompatibility locus from the deleted or translocated portion of the long arm of chromosome 6.     

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.     

Y;autosome translocations and mosaicism in the aetiology of 45,X maleness: assignment of fertility factor to distal Yq11

Summary Three 45,X males have been studied with Y-DNA probes by Southern blotting and in situ hybridization. Southern blotting studies with a panel of mapped Y-DNA probes showed that in all three individuals contiguous portions of the Y chromosome including all of the short arm, the centromere, and part of the euchromatic portion of the long arm were present. The breakpoint was different in each case. The individual with the largest portion (intervals 1–6) is a fertile male belonging to a family in which the translocation is inherited in four generations. The second adult patient, who has intervals 1–5, is an azoospermic, sterile male. These phenotypic findings suggest the existence of a gene involved in spermatogenesis in interval 6 in distal Yq11. The third case, a boy with penoscrotal hypospadias, has intervals 1–4B. In situ hybridization with the pseudoautosomal probe pDP230 and the Y chromosome specific probe pDP105 showed that Y-derived DNA was translocated onto the short arm of a chromosome 15, 14, and 14, respectively. One of the patients was a mosaic for the 14p+ translocation chromosome. Our data and those reported by others suggest the following conclusions based on molecular studies in eight 45,X males: The predominant aetiological factor is Y;autosome translocation observed in seven of the eight cases. As the remaining case was a low-grade mosaic involving a normal Y chromosome, the maleness in all cases was due to the effect of the testis determing factor, TDF. There is preferential involvement of the short arm of an acrocentric chromosome (five out of seven translocations) but other autosomal regions can also be involved. The reason why one of the derivative translocation chromosomes becomes lost may be that it has no centromere.     

Complex chromosomal rearrangement involving chromosomes 11, 13 and 21

In the present report we describe a complex chromosomal rearrangement, resulting in a distal 11p monosomy, in a 7-month-old severely retarded girl with a non-specific phenotype. In this complex chromosomal rearrangement chromosomes 11, 13 and 21 are involved in the translocation of the long arm of chromosome 21 on the short arm of chromosome 13 and translocation of the short arm and satellites of chromosome 21 on the short arm of chromosome 11.     

Molecular detection of a Yp/18 translocation in a 45,X holoprosencephalic male

Summary Prenatal diagnosis in a fetus with holoprosencephaly showed a 45,X karyotype and a suspected 18p abnormality. At birth, the fetus presented with normal male genitalia. Y chromatin was not cytogenetically detectable by Q-, G-, or G11-banding. Mosaicism for a cell line containing a Y chromosome was not observed in amniocytes, lymphocytes, or skin fibroblasts. Southern blot analysis for 11 different Y-DNA loci demonstrated the presence in the patient's genome of sequences derived from the short arm, centromeric region, and proximal long arm of the Y chromosome (intervals 1–5). The distal long arm of the Y (intervals 6 and 7) was absent. In situ hybridization with the Y-derived probe pDP105 showed silver grains over the short arm of the del(18) chromosome, suggesting a Y/18 translocation with loss of 18p and distal Yq material.     

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.     

Une triple translocation chez le Triton Pleurodeles waltlii

A cytogenetic study has lead us to a stock of fertile heterozygotes for a triple translocation. The chromosomal rearrangement has first been detected in a female resulting from a cross between a normal female and a male submitted to X ray-irradiation. The aberration consists of rearrangements between a chromosome 3, a chromosome 6 and a chromosome 7. Abnormal chromosomes have the following constitution: 7q?: the terminal portion of the long arm is lost and replaced by the end of the short arm of the chromosome 3. 6 q+: the terminal portion of the long arm is lost and replaced by the end of the long arm of the chromosome 7. 3p+: the terminal portion of the short arm is lost and replaced by the end of the long arm of the chromosome 6. On the analogy of the human chromosome standardization, the formula of heterozygotes is 24, t (3p+, 6q+, 7q?). The first meiotic division shows both in the female and in the male 9 bivalents and one hexavalent. The formulae of the gametes are the same in both sexes. When a heterozygote is bred with a normal individual the offspring is composed of phenotypically normal or abnormal animals, depending on their karyotypes. The unbalanced karyotypes are lethal or semilethal. The importance of the malformations depends on the temperature of the water where the animals grow. The study of the meiotic slides brings a cytological confirmation of the results obtained from the study of the phenotypes and karyotypes which appear in the offspring.