Analysis for common chromosomal breakpoint regions among 586 carriers of reciprocal translocations from Henan Province / 中华医学遗传学杂志

OBJECTIVE@#To determine the frequency, common chromosomal karyotypes and breakpoints, and involved regions among carriers of reciprocal translocations from Henan Province, and to explore the influence of common breakpoint regions on pregnancy and fetal development.@*METHODS@#For 586 carriers of reciprocal translocations, the above features were retrospectively analyzed.@*RESULTS@#The 586 reciprocal translocations were identified among 62 477 subjects, which yielded a frequency of 0.94%. Among these, 572 (0.92%) had abnormal fertility, and 14 (0.02%) had a history of abnormal fetal development. Statistical analysis showed that chromosomes 1, 4, 7 and 11 were most frequently involved, with t(11;22)(q25;q13) being the most common type of translocation. In total 437 breakpoint regions were identified, with 11q23, 22q13 and 1p36 being most frequently involved, which resulted in infertility, abortion, embryo death, congenital malformation, development delay, mental retardation or a normal phenotype.@*CONCLUSION@#Above results indicated a 0.92% carrier rate for reciprocal chromosomal translocations in Henan. The location of breakpoint regions may affect the pregnancy and/or fetal development. Discovery of such regions may enable more accurate genetic, reproductive and developmental counseling for carriers, and provide reference for delineation of function and pathogenetic mechanism of the relevant genes.

Clinical features of carriers of reciprocal chromosomal translocations involving chromosome 2: report of nine cases and review of the literature

ABSTRACT Objective: To explore the clinical features of carriers of chromosome 2 translocations, enabling informed genetic counseling of these patients. Materials and Methods: Eighty-two male carriers of a translocation who were infertile or receiving fertility counseling were recruited. Cytogenetic analyses were performed using G-banding. A search of PubMed was performed to determine whether the identified translocations on chromosome 2 are involved in male infertility. The relationships of translocation breakpoints with male infertility and recurrent pregnancy loss were analyzed. Results: Of the 82 translocation carriers, 9 (11%) were carriers of a chromosome 2 translocation. Four cases had oligozoospermia or infertility, while five had normal semen. In an analysis of the literature, 55 patients who were carriers of chromosome 2 translocations were also reviewed. Breakpoints at 2p13 and 2q31 were observed in six patients each, and were the most common. Breakpoints at 2p23, 2p13, 2p11.2, 2q31, and 2q37 were associated to both pre-gestational and gestational infertility, while other breakpoints were associated with gestational infertility. Conclusions: All breakpoints at chromosome 2 were correlated with gestational infertility. Carriers of chromosome 2 translocations should therefore receive counseling to continue with natural conception and use of different technologies available via assisted reproductive technology, such as preimplantation genetic diagnosis.

Retrospective karyotype study in mentally retarded patients / Estudo retrospectivo de cariótipo em pacientes com retardo mental

SUMMARY Objective: To describe the chromosomal alterations in patients with mental retardation (MR) using G-banding karyotype analysis. Method: A retrospective study of the results G-banding karyotype analysis of 369 patients investigated for MR was performed. Based on the structural rearrangements found, the authors searched all chromosomal regions related with breakpoints, and these were compared with the literature on MR and databases. Results: 338 (91.6%) normal cases, and 31 (8.4%) with some type of chromosomal abnormality were identified. Among the altered cases, 21 patients (67.8%) were identified with structural chromosomal alterations, nine (29%) with numerical alterations, and one (3.2%) with numerical and structural alterations. Conclusion: Structural chromosomal abnormalities were observed more frequently in this study. G-banding karyotyping contributes to the investigation of the causes of MR, showing that this technique can be useful for initial screening of patients. However, higher resolution techniques such as array based comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MPLA) can detect submicroscopic alterations commonly associated with MR.

RESUMO Objetivo: descrever as alterações cromossômicas em pacientes com retardo mental (RM) pela análise do cariótipo com bandas G. Método: foi realizado um estudo retrospectivo dos resultados de cariótipo com bandas G de 369 pacientes em investigação de RM. A partir dos rearranjos estruturais encontrados, foram levantadas todas as regiões cromossômicas envolvidas nos pontos de quebra e elas foram comparadas com a literatura para RM e bancos de dados. Resultados: foram identificados 338 (91,6%) casos normais e 31 (8,4%) com algum tipo de alteração cromossômica. Dentre os casos alterados, 21 pacientes (67,8%) foram identificados com alterações cromossômicas estruturais, 9 (29%) com alterações numéricas e 1 (3,2%) com alteração numérica e estrutural. Conclusão: as alterações cromossômicas estruturais foram aquelas observadas com maior frequência. O cariótipo com bandas G contribui para a investigação das causas de RM, mostrando que essa técnica pode ser útil como uma primeira triagem dos pacientes. No entanto, técnicas mais resolutivas como o array based comparative genomic hibridization (aCGH) e o multiplex ligation dependent probe amplification (MLPA) permitem detectar alterações submicroscópicas comumente associadas ao RM.

Diversity of breakpoints of variant Philadelphia chromosomes in chronic myeloid leukemia in Brazilian patients

Background: Chronic myeloid leukemia is a myeloproliferative disorder characterized by the Philadelphia chromosome or t(9;22)(q34.1;q11.2), resulting in the break-point cluster regionAbelson tyrosine kinase fusion gene, which encodes a constitutively active tyrosine kinase protein. The Philadelphia chromosome is detected by karyotyping in around 90% of chronic myeloid leukemia patients, but 5-10% may have variant types. Variant Philadelphia chromosomes are characterized by the involvement of another chromosome in addition to chromosome 9 or 22. It can be a simple type of variant when one other chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. Few studies have reported the incidence of variant Philadelphia chromosomes or the breakpoints involved among Brazilian chronic myeloid leukemia patients. Objective: The aim of this report is to describe the diversity of the variant Philadelphia chromosomes found and highlight some interesting breakpoint candidates for further studies. Methods: the Cytogenetics Section Database was searched for all cases with diagnoses of chronic myeloid leukemia during a 12-year period and all the variant Philadelphia chromosomes were listed. Results: Fifty (5.17%) cases out of 1071 Philadelphia-positive chronic myeloid leukemia were variants. The most frequently involved chromosome was 17, followed by chromosomes: 1, 20, 6, 11, 2, 10, 12 and 15. Conclusion: Among all the breakpoints seen in this survey, six had previously been described: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 and 17q21. The fact that some regions get more fre- quently involved in such rare rearrangements calls attention to possible predisposition that should be further studied. Nevertheless, the pathological implication of these variants remains unclear. .

Characteristics of complex chromosomal rearrangement in Chinese male carriers and its impact on male fertility / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of complex chromosomal rearrangement (CCR) in Chinese male carriers and its influence on male fertility.</p><p><b>METHODS</b>Using the G band technique, we conducted karyotype analysis on the peripheral blood lymphocytes of 1,625 Chinese males with reproductive problems. We also searched CNKI and Wanfang database for CCR-related literature published between January 1984 and November 2013, followed by statistical analysis on the CCR characteristics and reproduction-related data of the CCR carriers.</p><p><b>RESULTS</b>Two CCR carriers were found among the 1,625 males and another 47 cases identified from the databases. Among the 49 CCR carriers, there were 17 three-way exchange cases (34.7%), 17 double two-way exchange cases (34.7%), and 15 exceptional cases (30.6%), with no statistically significant differences in the incidence of the three types (P > 0.05). Azoospermia- or oligospermia-induced infertility was found in 19 (38.8% ) of the CCR carriers. A total of 87 pregnancies were achieved in the other 30 (61.2%), among which spontaneous abortion occurred in 75.9% (66/87), dead fetus and malformed infant death in 9.2% (8/87), and phenotypically normal offspring in 14.9% (13/87). Recurrent abortion was associated frequently with breakpoints on CCR-involved chromosomes 6, 7, 8, 11, and 16, while dyszoospermia mostly with breakpoints on CCR-involved chromosomes 10 and 14. The breaking occurred more than 3 times at 1p22, 1q25, 2q31, 5p13, 5q35, 6q23, 8q13, and 20p13. Moreo- ver, the breakpoints at 2q31, 5q35, and 8q13 were particularly related to recurrent abortion, while that at 1p22 only to dyszoospermia.</p><p><b>CONCLUSION</b>CCR is extremely rare. Male CCR carriers are often identified through reproductive problems and have high risks of infertility and abnormal pregnancy and a very low rate of normal newborns. In addition, chromosomes and breakpoints involved in CCR may affect the fertility of male CCR carriers, and some particular chromosomal breakpoints may play a key role in gametogenesis.</p>

Meiotic analysis of spermatogenic cells in severe oligoasthenoteratozoospermia with chromosome 13 rearrangement / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the possible mechanisms of spermatogenic arrest in severe oligoasthenoteratozoospermia induced by supernumerary, ring-neocentric 13q12.3 --> 13q22 chromosome and reciprocal deletion.</p><p><b>METHODS</b>We performed a genomic-wide high-density oaCGH analysis for a case of oligoasthenoteratozoospermia with abnormal chromosome 13 to characterize the breakpoints of the chromosome involved or the gene deletion caused by the rearrangement. We also conducted a fluorescence in situ hybridization analysis on the germ cells using probes of 13q14/13qter to observe the pairing condition of homologous chromosome 13.</p><p><b>RESULTS</b>We identified by oaCGH analysis a microdeletion of 4 consecutive probes (A_16_P19757882, A_16_P02744617, A_14_ P108858 and A_16_P02744687 at chr13q12.3: 27979261 --> 28039191) with 59.93 kb between the FLT1 and POMP genes, with no annotated genes in the deleted region. The signals of 13q14 and 13qter were separated from each other in 90% of all the primary spermatocytes examined, indicating the unpairing of homologous chromosome 13 or synapse failure.</p><p><b>CONCLUSION</b>Chromosomal rearrangement-induced spermatogenesis failure is caused by the unpairing of the homologous chromosomes involved in the first meiotic division of germ cells.</p>

A Case of Partial Monosomy 10q with Partial Trisomy 22q due to Maternal Balanced Translocation

Partial monosomy of chromosome 10q is a rare chromosomal anomaly. Most cases of partial deletion 10q have chromosome breakpoints in the 10q25 or 10q26 region. Recently about 30 cases with breakpoint in the 10q26 region have been reported. Partial trisomy of chromosome 22q is also a rare chromosomal anomaly. Most cases of partial duplication 22q are 22q proximal segment duplications known as Cat-eye syndrome. The other cases, 22q11.2 microduplications and 22q distal long arm (22qter) duplications, are also reported but exceedingly rare. We experienced a male neonate who had facial dysmorphisms, congenital heart defect and cryptorchidism. His chromosomal analysis revealed an deletion of chromosome 10q26.1-->qter and duplication of chromosome 22q11.2-->qter caused by maternal balanced translocation e.g. partial monosomy 10q and partial trisomy 22q. Although some cases of partial monosomy 10q were accompanied by other chromosomal abnormalities, this combination of chromosomal abnormalities has not been reported in the literature.

1-beta-D-Arabinofuranosyl-cytosine Induces Chromosomal Breaks in vitro

PURPOSE: Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-beta-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. METHODS: T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. RESULTS: Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. CONCLUSIONS: S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.