Partial trisomy of 13(pter→q12) due to 47,XY,+der(13),t(13;22)(q12;q13)mat

Summary A 36-month-old boy presented with short stature, short neck, shield-shaped chest, and mental retardation. Chromosome analysis showed trisomy for the short arm and the proximal portion of the long arm of chromosome 13 [47,XY,+der(13),t(13;22)(q12;q13)mat]. The patient's mother has a balanced translocation between the long arms of chromosomes 13 and 22 [46,XX,t(13;22)(q12;q13)]. The patient's neutrophils showed an elevated number of nuclear projections and his fetal hemoglobin level was undetectable.     

47,XY,+der(11;22)(q23;q12) following balanced translocation t(11;22)(q23;q12)mat

Summary Report of a supernumerary extra chromosome der(11;22)(q23; q12) resulting from a balanced translocation in the mother. The propositus suffers from mental deficiency, deafness and extreme muscular weakness and exhibits cleft palate, a labial lymphangioma and an atrial septum defect. Since the features of partial trisomy 11q23 frequently associated with a translocation t(11q;22q) bear similarities with the cases of so called trisomy 22 one might conjecture that some of these observations are in fact products of translocations including partial 11q.     

Familial translocation t(10;21)(q22;q22)

Summary A family is described with a translocation t(10;21)(q22;q22) transmitted through three generations. This family was studied for the apparition of several miscarriages and two sisters with multiple malformations. Both children had a probably partial trisomy of chromosome 10 and a monosomy of chromosome 21 due to a maternal adjacent-2 meiotic segregation.     

Predisposition for breast cancer in carriers of constitutional translocation 11q;22q.

A translocation between the long arms of chromosomes 11 and 22, t(11;22)(q23;q11), is the most frequent constitutional reciprocal translocation in man. This chromosome abnormality has not previously been reported to be associated with an increased risk for neoplasia. The observation of one patient with a constitutional translocation t(11q;22q) and breast cancer prompted us to study the relationship between these two conditions. The incidence of breast cancer was determined in carriers of t(11q;22q). The karyotypes were determined by QFQ-banding, and the breakpoints were then further characterized by fluorescent in situ hybridization. Eight families with a total of 22 balanced carriers were found. In five of these families there was one case of breast cancer each. In another family a case of an unknown malignancy was reported in one member. No other malignancies were found among these patients. The number of breast cancer cases was significantly higher than expected among the translocation carriers (P < .001). The chromosomal breakpoints showed the same localization with the markers used, in the seven families studied. The association of constitutional translocation t(11q;22q) and breast cancer identifies a subset of patients with a highly increased risk for breast cancer who would benefit from counseling and screening. It also suggests the involvement of genes on 11q and/or 22q, in the tumorigenesis of breast cancer.     

Pure 4p trisomy due to a de novo 4q;22p dicentric translocated chromosome karyotype 46,XX,-22,+t(4;22)(q1200;p13).

A de novo t(4;22)(q1200;p13) is reported in a girl with a florid 4p trisomy phenotype. The abnormal chromosome was identified by high resolution, C-bands and confirmed by 5-BrdU as de novo dicentric translocated chromosome.     

Familial aniridia and translocation t(4;11)(q22;p13) without Wilms' tumor

A family with dominantly inherited aniridia in three generations is presented. All three patients had an apparently balanced chromosome translocation t(4;11)(q22;p13). The patients were otherwise clinically normal and without signs of Wilms' tumor; their erythrocyte catalase activities were within the normal range. We suggest that in this family aniridia is caused either by a submicroscopic deletion at the translocation breakpoint 11p13 or by a position effect on the same chromosome segment. Furthermore, the loci for aniridia and Wilms' tumor susceptibility are separate. It follows that the WAGR complex is caused by a mutation of more than one gene located at 11p13. The theoretical implications of a presumably defective allele causing a mendelian dominant phenotype are discussed.     

Trisomy 13 with a 13q14q translocation.

A sporadic case of Patau syndrome with 46,XY,14-,t(13q14q)+ karyotype is reported in a 2-month-old child. Dermatoglyphic and cytogenetic findings of the propositus and cytogenetic study of his parents are presented.     

Pachytene analysis in males heterozygous for a familial translocation (9;12;13) (q22; q22; q32) ascertained through a child with partial trisomy 9

A family with four male and three female heterozygotes for a three-way translocation (9;12;13) (q22; q22; q32) in three generations was ascertained through a chromosomally imbalanced newborn with an additional derivative chromosome 9 resulting from nondisjunction. Three heterozygous males from two generations with apparent differences in their fertility status were investigated using pachytene spreads and testicular histology. Pachytene analysis in all three individuals, the fertile (II-2) as well as the subfertile (III-7) and infertile (III-9), showed a hexavalent with central nonpairing around the translocation breakpoints in nearly all spermatocytes. Thus, the observed hexavalent configurations in pachytene do not seem to have caused impaired fertility. This rather may have been the result of sperm carrying unbalanced chromosome sets. However, the observed difference in fertility between the heterozygous fertile male in generation II and his two heterozygous sons remains unexplained.     

Mapping of the human gene for epidermal growth factor receptor (EGFR) on the p13 leads to q22 region of chromosome 7

We previously reported that the structural gene for epidermal growth factor receptor (EGFR) can be mapped to the p22 leads to qter region of human chromosome 7 (Shimizu et al., 1979, 1980). In the present study, we produced two series of human-mouse cell hybrids by fusing mouse A9 cells that are deficient in EGFR with the human diploid fibroblast lines GM1356, 46,XX,t(1;7)(p34;p13), and GM2068, 46,XX,t(6;7)(q27;q22), both of which possess EGF receptors. Expression of EGF binding ability in the former series of cell hybrids was correlated with the retention of the human translocation chromosome containing the 7p13 leads to qter region, and in the latter series of cell hybrid it was correlated with the retention of the human translocation chromosome containing the 7pter leads to q22 region. Therefore, the EGFR gene can be localized in the p13 leads to q22 region of chromosome 7.     

Evidence that chromosome band 22q12 is concerned with cell proliferation in chronic myeloid leukaemia

Summary A man and two of his three children carried an abnormally short chromosome 22 resembling the Philadelphia chromosome (Ph¹). Giemsa banding showed that the abnormal chromosome resulted from a translocation t(11;22) (q25;q13). The breakpoint on chromosome 22 was at the q12/q13 band interface compared with the breakpoint of Ph¹ at the q11/q12 band interface. The absence of leukaemia or haematological disorder in members of this family suggests that the critical genetic site on chromosome 22 concerned with abnormal myeloid cell proliferation in human leukaemia is contained in the 22q12 band.     

The phenotype in partial 13q trisomies,apropos of a familial (13;15)(q22;q26) translocation

Summary A 12 month-old male patient with a karyotype 46, XY,-15,+der(15),t(13;15)(q22;q26)pat is presented. His stillborn sib showed malformations compatible with the 13q deletion syndrome, probably due to a 46,XY, der(13) karyotype. Phenotypic analysis of 41 cases from the literature with partial distal 13q (D13q) trisomies indicate that the segment 13q22 qter in trisomy with or without another concomitant aneusomy is sufficient to produce the majority of the trisomy 13 syndrome features, some of which (cleft palate, increased HbF and projections in PMN) are present in different non-overlapping partial 13q trisomies. About 82% of the D13q trisomies are inherited, more frequently from the mother.     

A novel translocation,t(9;21)(q13;q22) rearranging the RUNX1 gene in acute myelomonocytic leukemia

A novel translocation t(9;21)(q13;q22) associated with trisomy 4 has been detected in a patient with acute myelomonocytic leukemia (AML,M4) in relapse. The chromosomal translocation results in rearrangement of the RUNX1 gene at 21q22. The DNA sequence rearranged on chromosome 9 remains unidentified. The diversity of the partners involved in translocations implicating RUNX1 suggests that the functional consequences of the abnormality are more due to the truncation of RUNX1 than to the identity of its partner in the rearrangement.     

Unexpected Inheritance of a Balanced Homologous translocation t(22q;22q) from father to a phenotypically normal daughter

Rearrangements between homologous chromosomes are extremely rare and manifest mainly as monosomic or trisomic offsprings. There are remarkably few reports of balanced homologous chromosomal translocation t (22q; 22q) and only two cases of transmission of this balanced homohologous rearrangement from mother to normal daughter are reported. Robersonian translocation carriers in non-homologous chromosomes have the ability to have an unaffected child. However, it is not possible to have an unaffected child in cases with Robersonian translocations in homologous chromosomes. Carriers of homologous chromosome 22 translocations with maternal uniparental disomy do not have any impact on their phenotype. We are presenting a family with a history of multiple first trimester miscarriages and an unexpected inheritance of balanced homologous translocation of chromosome 22 with paternal uniparental disomy. There are no data available regarding the impact of paternal UPD 22 on the phenotype. We claim this to be the first report explaining that paternal UPD 22 does not impact the phenotype.     

Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families

The t(11;22) is the only known recurrent, non-Robertsonian constitutional translocation. We have analyzed t(11;22) balanced-translocation carriers from multiple unrelated families by FISH, to localize the t(11;22) breakpoints on both chromosome 11 and chromosome 22. In 23 unrelated balanced-translocation carriers, the breakpoint was localized within a 400-kb interval between D22S788 (N41) and ZNF74, on 22q11. Also, 13 of these 23 carriers were tested with probes from chromosome 11, and, in each, the breakpoint was localized between D11S1340 and APOA1, on 11q23, to a region 相似文献   

Patau's syndrome and 13q21q translocation

Summary This paper reports the case of a one-day-old male child presenting the typical features of Patau's syndrome. The cytogenetic study by means of conventional techniques and GTG and QFQ banding techniques showed that the chromosomal pattern of the propositus was 46,XYq+,-21,+t(13q21q) 15ps+,22ps+, and that the nondisjunction that originated the translocation and trisomy had occurred in the mother.     

A Case of ABL-BCR Negative, Philadelphia Positive CML with t(5;9)(q13;q34)

The Philadelphia chromosome is found in more than 90 percent of chronic myeloid leukemia (CML) patients. In most cases, it results from the reciprocal t(9;22)(q34;q11), with the ABL proto-oncogene from 9q34 fused to the breakpoint cluster region (BCR) locus on 22q11. In 5 to 10 percent of patients with CML, the Ph originates from variant translocations, involving various breakpoints in addition to 9q34 and 22q11. Here we report a rare case of a Philadelphia positive CML patient carrying t(5;9)(q13;q34) and deletion of ABL/BCR on der(9) as a separate event.     

Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC) clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a variation of the breakpoint position between patients. In 22q11, we have sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region; these contain low copy repeats (LCRs). Southern blot analysis with probes from BAC2280L11 has revealed different patterns between normal controls and translocation carriers, indicating that sequences similar/identical to these probes flank the translocation breakpoint. The occurrence of LCRs has previously been associated with genomic instability and "unclonable" regions. Hence, the presence of such repeats renders standard translocation breakpoint cloning techniques ineffective. Thus, we have used high resolution fiber-FISH to study this region in normal and translocation cases by using probes from 22q11, LCRs and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we have localised the breakpoint in 22q11 to approximately 20-40 kb from the centromeric border of the LCR (i.e. the telomeric end of AC006547) and have confirmed the breakpoint position on 11q23.     

Proximal trisomy 13q and distal monosomy 8p in a dysmorphic and mentally retarded patient with an isodicentric chromosome 13q and a 13q/8p translocation chromosome

A 40 year-old dysmorphic and mentally retarded female is reported with a de novo unbalanced chromosomal rearrangement (karyotype: 46,XX,der(8)t(8;13)(p23;q123),idic(13)(pter-->q123: q123-->pter) resulting in an isodicentric chromosome 13 and a double aneusomy including partial trisomy 13 (13pter-q123) and distal monosomy 8p (8pter-p23). The main clinical findings consist of developmental/mental retardation, behavioural disturbances and minor congenital defects, not consistent with the clinical pattern of either of the two aneusomies. A mechanism for the chromosome rearrangement is proposed and the absence of specific physical findings in the present patient is discussed in the light of the available literature data.     

Transmission of a t(13q22q) chromosome observed in three generations with segregation of the translocation D1-trisomy syndrome.

A case of an inherited type of D/G translocation D1-trisomy syndrome was described. A female proposita who had the clinical signs of D1-trisomy syndrome was found to have a chromosome complement of 46,XX,--G,+t(DqGq). examination of Q- and G-stained karyotypes revealed that the chromosomes involved in the translocation were members of Nos. 13 and 22, or t(13q22q) with breaks at p12 of both chromosomes. C-stained figures also showed a large heterochromatin block in its centromeric region. The t(13q22q) chromosome was transmitted from the paternal grandmother of the proposita through at least three generations.     

Localization of human c-mos to chromosome band 8q11 in leukemic cells with the t(8;21) (q22;q22)

Summary Chromosome in situ hybridization studies locate c-mos to chromosome band 8q11 in leukemic cells carrying the t(8;21) (q22;q22). This amends the previous assignment of c-mos to chromosome band 8q22 and conforms with its recent assignment to 8q11 in normal cells and in a cell line with a structurally abnormal chromosome 8. C-mos lies proximally to, and distant from, the breakpoint at 8q22 in the t(8;21) and is unlikely to have a role in the onset of acute myeloid leukemia characterized by this translocation.