Philadelphia chromosome positive chronic myelocytic leukemia with a complex translocation, t(4;9;22)(q31;q34;q11) and long survival.

An 8;21 translocation with duplication of the der(21) is described in a 72-year-old man who presented with features of chronic myelomonocytic leukemia. Progression to acute myelomonocytic leukemia occurred within one month of diagnosis. The possible prognostic significance of the t(8;21) with duplicated der(21) in myelodysplasia is discussed.     

Analysis of human sperm chromosome complements from a male heterozygous for a reciprocal translocation t(11;22)(q23;q11)

A reciprocal translocation between chromosomes 11 and 22 (t(11;22)(q23;q11)) is a site-specific translocation that is of particular interest because of the propensity for 3:1 segregation of the chromosomes during meiosis. There have been no published reports of chromosomally unbalanced offspring born as a result of adjacent 1 or 2 meiotic segregations in a heterozygote for this translocation. This could be explained by a meiotic mechanism which produces only 3:1 chromosomal segregations or by differential embryonic survival in which 2:2 adjacent segregations do not produce a viable pregnancy. To distinguish between these two possibilities, sperm chromosome complements from a man heterozygous for this 11;22 translocation were studied. The human sperm chromosomes were analysed after fertilization of zona pellucida-free golden hamster eggs. All possible 2:2 (alternate, adjacent 1, adjacent 2) and 3:1 segregations were observed and these segregations occurred in approximately equal frequencies. The frequency of other chromosome abnormalities, unrelated to the translocation, did not appear to be increased. These results indicate that the 11;22 translocation does not specifically cause 3:1 disjunction of chromosomes but that this segregation of chromosomes is more likely to result in a viable pregnancy.     

Chronic myeloid leukemia with a rare variant Philadelphia translocation: t(9;10;22)(q34;q22;q11)

Cytogenetic studies were conducted on 30 pituitary adenomas, using both direct and/or short-term in vitro culture methods. An apparently normal chromosome complement was found in 14 tumors; 5 adenomas were characterized by hyperdiploid or near-triploid modal chromosome numbers. Recurrent numerical deviations were identified in 12 samples, which primarily involved gains of chromosomes 4, 7, 8, 9, 12, and 20 by gains, and losses of chromosomes 10, 14, 19, and 22. Four adenomas were shown to have structural chromosome rearrangements with no apparent recurrent pattern of involvement.     

Partial deletion of long arm of chromosome 11: del (11) (q23)

The cytogenetic analysis of an infant with multiple congenital anomalies revealed a small deletion of the long arm of one No. 11 chromosome: 46,XX,del(11)(q23). The main clinical manifestations included: ocular colobomata, absent philtrum, severe congenital heart disease, contractures of the large joints and skin pigmentation. Both parents showed a normal chromosome constitution. In comparison to the previously reported cases of 11q-, the patient presented here had more severe congenital anomalies. The correlation of the size of the deletion, and the location of the break, with the physical findings is discussed.     

Homozygosity for a Y/22 chromosome translocation: t(Y;22) (q12;p12/13)

A newborn girl, homozygous for a balanced Y/22 chromosome translocation is described. This unique karyotype was detected during prenatal chromosome studies in the first pregnancy of a 26-year-old woman. Amniocentesis was performed because of clinical evaluation of severe fetal growth retardation in the 28th week of gestation. The cytogenetic results were confirmed using a lymphocyte culture after birth in the 30th week. Subsequent chromosome studies of the parents were hampered by the fact that the pregnancy was thought to be the result of artificial insemination with donorsperm. Nevertheless both, consanguineous, parents were shown to be carriers of the same, singular, chromosome translocation and the spermdonor could be excluded from paternity by bloodgroup- and HLA studies. Distamycin-A-DAPI chromosome staining and DNA studies of the mother were used to confirm the involvement of the Y-chromosome in this translocation. The probanda is developing quite normally at the age of 21 months.     

Involvement of a palindromic chromosome 22-specific low-copy repeat in a constitutional t(X; 22)(q27;q11)

Segmental duplications or low-copy repeats (LCRs) on chromosome 22q11 have been implicated in several chromosomal rearrangements. The presence of AT-rich regions in these duplications may lead to the formation of hairpin structures, which facilitate chromosomal rearrangement. Here we report the involvement of such a low-copy repeat in a t(X;22) associated with a neural tube defect. Molecular analysis of the chromosomal breakpoints revealed that the chromosome 22 breakpoint maps in the palindromic non-AT-rich NF1-like region of low-copy repeat B (LCR-B). No palindromic region was encountered near the breakpoint on chromosome X. Our findings confirm that there is no single mechanism leading to translocations with chromosome 22q11 involvement. Because LCR-B does not contain genes involved in neural tube development, we believe that the gene responsible for the observed phenotype is most likely localized on chromosome X.     

Double chromosome anomaly: Interstitial deletion 5q and reciprocal translocation (1;11) (p22;q21)

We describe a girl with multiple congenital abnormalities and developmental delay; her karyotype showed an apparently balanced translocation between the short arm of chromosome 1 and the long arm of chromosome 11, and an interstitial deletion of the long arm of chromosome 5 (q15q31). The clinical findings are compared with those described in other cases of 5q deletion, and the origin of the chromosome rearrangements is briefly discussed.     

Proximal duplication of the long arm of chromosome 10 (10q11.2 → 10q22): a distinct clinical entity

This report summarizes the clinical and cytogenetic findings in a 16-year-old moderately mentally retarded girl with 10q11.2----10q22 duplication. The phenotypic findings are identical to those found in one other patient with the same autosomal duplication. These data suggest that proximal 10q11.2-10q22 duplication is associated with a specific clinically recognizable syndrome.     

Site-specific reciprocal translocation,t(11;22) (q23;q11), in several unrelated families with 3:1 meiotic disjunction

We have studied 32 unrelated families with a site-specific reciprocal translocation between chromosomes 11 and 22 [t(11;22) (q23;q11)]. In translocation heterozygotes 3:1 meiotic segregation occurs and results in abnormal progeny who carry the der(22) as a supernumerary chromosome. Phenotypic findings consistent with 47,XX (or XY), +der(22), t(11;22) include mental retardation, preauricular skin tag and/or sinus, ear anomaly, palate anomaly, micrognathia, congenital heart disease, and genital anomalies in males. The frequency of abortions among offspring of male and female heterozygotes is increased. Segregation analysis shows that the risk for unbalanced offspring to be born to female heterozygotes may be as high as 10%, and that there may be a significant risk to male heterozygotes as well. The overall carrier frequency among progeny of 11;22 translocation carriers is 70.6%. The occurrence of multiple 11;22 translocation events is supported by de novo occurrence of the translocation, familial heteromorphic variants of the der(22), and varied racial and ethnic backgrounds of the families. To our knowledge, with the exclusion of centric fusion translocations, this represents the only example of nonrandom exchange in a constitutional chromosomal rearrangement.     

Sperm analysis by FISH in a case of t(17; 22) (q11; q12) balanced translocation: case report

Individual sperm from men with balanced translocations have different chromosomal contents. Thus, an estimation of the overall sperm chromosomal imbalance of such patients could help to give the couple an adapted genetic counselling. We report here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose reproductive history reported four miscarriages. Moreover, he had an abnormal semen analysis with oligoteratozoospermia. The meiotic segregation pattern was examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen percent of the sperm had balanced translocations or were normal. All other sperm were unbalanced (81%) and their distribution was observed as follows: the frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and 46.8% respectively. Among the segregations scored, 13.7% were related to second meiotic division abnormalities. Less than 2% of the total sperm scored were not explained. The 3:1 segregation was present at a very high rate, which is very unusual. In cases of balanced translocations, we believe that no general features can be drawn. Thus, the FISH technique may be very helpful for genetic counselling, which remains an important step and must be done with care.     

Frontonasal malformation and reciprocal translocation t(15;22)(q22;q13)

Trisomy 13 is very rare in live-born children. Only a small number of these children survive the first year and very few cases are reported to live longer. Survival time depends partly on the cytogenetic findings - full trisomy 13 or trisomy 13 mosaicism - and partly on the existence of serious somatic malformations. We report on a 11-year-old girl with full trisomy 13. In this case, missing cerebral and cardiovascular malformations probably allowed the long survival.     

Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2.

We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father.     

Sperm chromosome analysis in the father of a child with a de-novo reciprocal translocation t(11;15)(q12;q22) by G-banding and fluorescence in-situ hybridization

Analysis of sperm chromosomes by G-banding and two-colour fluorescence in-situ hybridization (FISH) was carried out in the father of a child with a de-novo reciprocal translocation t(11;15)(q12;q22). Sperm chromosome complements were obtained after in-vitro fusion of zona-free hamster oocytes and donor spermatozoa. A total of 112 sperm complements was first analysed by G-banding. The frequency of structural chromosome aberrations (9.8%) and the conservative frequency of aneuploidy (0.0%) were not significantly different from those obtained in our control donors. The proportions of X-bearing (53.2%) and Y-bearing (46.8%) spermatozoa were not significantly different from the expected 1:1 ratio. A total of 313 sperm complements was analysed by two-colour FISH. The frequency of structural abnormalities for chromosomes 11 and 15 was 3.2 and 0.3% respectively. The frequency of rearrangements for chromosome 11 was statistically significant when compared with control donors (0.4%) (P < 0.0001). No spermatozoa with the t(11;15)(q12;q22) translocation were observed, showing no evidence for a germ-cell mosaicism. These results suggest that the de-novo involvement of chromosome 11 in a structural rearrangement is not random, and that in this patient an increased risk of de-novo structural chromosome abnormalities in further offspring does exist.