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Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

t(13;15) and t(14;15) are two rare Robertsonian translocations. Meiotic segregation was studied in four males heterozygous for the rare Robertsonian translocations t(13;15) and t(14;15). Both locus-specific probes (LSPs) and whole chromosome painting (WCP) probes, specific to chromosomes 13, 14 and 15, were used in this study. The number of spermatozoa scored for each carrier ranged from 891 to 5000. The frequencies of normal and balanced sperm resulting from the alternate mode of segregation ranged from 77.6 to 92.8%, confirming the prevalence of alternate segregation over other segregation modes in all Robertsonian translocations. The incidences of unbalanced complements ranged from 6.7 to 20.4%, with a significant excess of disomy rates over the complementary frequencies of nullisomy. This variability might reflect differences in the location of breakpoints in translocated chromosomes, leading to the variable production of unbalanced gametes and the variable alterations of semen parameters in Robertsonian translocation carriers. [ABSTRACT FROM AUTHOR]

BACKGROUND: The t(14;22) remains one of the rare Robertsonian translocations observed in human, with an occurrence estimated at 1.2%. Three cases of rare Robertsonian translocation t(14;22) were investigated for meiotic segregation in sperm samples from male carriers using the fluorescent in situ hybridization (FISH) procedure. The three carriers included two men with an abnormal semen analysis and one with normal semen parameters. METHODS: Both locus-specific probes and whole-chromosome painting probes, specific for chromosomes 14 and 22, were used in this study. The number of spermatozoa scored for each probe set ranged from 3279 to 10 024. RESULTS: In the three carriers, similar frequencies, ranging from 78.53 to 81.76%, were found for normal and balanced spermatozoa resulting from alternate segregation. The total proportion of unbalanced spermatozoa resulting from adjacent modes of segregation ranged from 17.59 to 20.94%. CONCLUSION: This finding confirmed the predominance of alternate segregation over other segregation types in all Robertsonian translocations and indicates a higher production of imbalances in the t(14;22) than in most of the Robertsonian translocations previously analysed. This could be related to the variable location of breakpoints in Robertsonian translocations. This breakpoint diversity could also play a role in the differences in reproductive status observed in male carriers of Robertsonian translocations. [ABSTRACT FROM AUTHOR]

BACKGROUND: The t(13;22) Robertsonian translocation constitutes a rare form of rearrangement between acrocentric human chromosomes. Most of the meiotic segregation studies of human Robertsonian translocations have been performed on common t(13;14) and t(14;21) translocations. Analysis of the chromosomal constitution in sperm of Robertsonian translocation carriers is of great interest for assessing the risk of unbalanced forms and adapting genetic counselling. In the present study, we present the first meiotic segregation study of a t(13;22) Robertsonian translocation in human sperm. METHODS: A total of 11 787 sperm nuclei were scored using two distinct FISH labelling techniques, i.e. the locus-specific probes (LSI) method and the whole chromosome painting (WCP) technique. RESULTS: The frequency of normal or balanced sperm resulting from alternate meiotic segregation was 86%. Incidences of unbalanced complements resulting from adjacent segregation modes were 12.79% and 14.36% in LSI and WCP assays, respectively. No significant excess of nullisomy or disomy for the affected chromosomes was observed. CONCLUSIONS: Similar results in segregation were obtained with the two techniques, demonstrating the efficiency of the two strategies for the direct segregation analysis of Roberstsonian translocations. The results obtained indicated a moderate meiotic production of imbalance. This study shows that the rare Robertsonian translocation (13;22) displays a similar distribution of balanced and unbalanced sperm patterns as the common Robertsonian translocations previously studied. This suggests that the behaviour of acrocentric chromosomes was similar in all cases of centric fusion. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the homozygous NACHT, leucinerich region and pyrin domains-containing protein family 7 (NLRP7) mutations in a Moroccan woman with recurrent reproductive failure.

Objective: Paracentric inversions (PAI) are structural chromosomal rearrangements generally considered to be harmless. To date, only a few studies have been performed concerning the meiotic segregation of these rearrangements, using either the human--hamster fertilization system or fluorescence in-situ hybridization (FISH) with centromeric or telomeric DNA probes. In order to improve the assessment of imbalances in paracentric inversions, we present a new strategy based on the use of BAC probes that allow a precise localization of chromosome breakpoints and the identification of all meiotic products in human spermatozoa. Materials/Methods: Three cases of paracentric inversion were thus investigated in sperm samples: an inv(5)(q13.2q33.1), an inv(9)(q21.2q34.13), and an inv(14)(q23.2q32.13). The breakpoint spanning BAC were used along with the BAC in contigs for sperm FISH. Sperm nuclei were decondensed using 0.5M NaOH solution. Sperm analysis was performed by multicolour FISH. Results: A total of 4807, 1608 and 7670 sperm nuclei were evaluated for inv(5), inv(9) and inv(14), respectively. In each case, the frequencies of sperm harbouring normal, inverted, duplicated/deficient and dicentric chromosomes were determined. The global rate of recombinants was 9.69%, 12.55% and 3.72%, respectively. All the breakpoints were found to be in G light regions. Conclusion: The meiotic behaviour of chromosomal paracentric inversions has hardly been explored in man. The technical difficulties inherent to the precise identification of all meiotic products in paracentric inversions constitute important limitations for accurate segregation analysis. Here, we demonstrate that BAC clones spanning the breakpoints can be efficiently used as probes for directly determining the segregation pattern of chromosomal inversions in human sperm. Of course, such an in-situ mapping of breakpoints is labour-intensive and takes longer than the use of commercial centromeric and subtelomeric probes. As a result of this effort to use BAC probes, a complete and precise segregation analysis can be carried out, which allows all possible segregants from each recombination mechanism described in paracentric inversions to be distinguished, and thus excludes the possibility of missing out segregants. These detailed data might contribute to a better exploration of the meiotic behaviour of paracentric inversions, and they might also significantly improve the genetic counselling provided to inversion carriers. [ABSTRACT FROM AUTHOR]