Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review

International audienceObjective: To review the discovery of chromothripsis and analyze its impact on human reproduction.Design: Database and literature analysis.Setting: University hospital.Patient(s): Carriers of massive and complex chromosomal rearrangements.Intervention(s): Cytogenetic analysis and molecular testing (fluorescence in situ hybridization, microarray, whole-genome sequencing).Main outcome measure(s): Chromothripsis occurrence in human gametes and preimplantation embryos, with regard to the potential causative mechanisms described in literature.Result(s): Databases were searched for the literature published up to March 2014. Chromothripsis is characterized by the shattering of one (or a few) chromosome segments followed by a haphazard reassembly of the fragments generated, arising through a single initial catastrophic event. Several mechanisms involving abortive apoptosis, telomere erosion, mitotic errors, micronuclei formation, and p53 inactivation might cause chromothripsis. The remarkable point is that all these plausible mechanisms have been identified in the field of human reproduction as causal factors for reproductive failures and the genesis of chromosomal abnormalities. Specific features of gametogenesis and early embryonic development such as the weakness of cell cycle and mitosis checkpoints and the rapid kinetics of division in germ cells and early cleavage embryos may contribute to the emergence of chromothripsis.Conclusion(s): The discovery of this new class of massive chromosomal rearrangement has deeply modified our understanding on the genesis of complex genomic rearrangements. Data presented in this review support the assumption that chromothripsis could operate in human germlines and during early embryonic development. Chromothripsis might arise more frequently than previously thought in both gametogenesis and early human embryogenesis

Développement d'un endomicroscope non linéaire pour l'observation in vivo in situ de la matrice extracellulaire des tissus pulmonaires

A first review of the InVivo-ONL project is presented. The aim of the project is to develop a non-linear endomicroscopic system dedicated in first intention to in vivo imaging of the lung extracellular matrix

Mosaic complete tetrasomy 21 in a fetus with complete atrioventricular septal defect and minor morphological variations

BACKGROUND: Tetrasomy 21 is a very rare aneuploidy which could clinically resemble a Down syndrome. It was most often described in its partial form than complete. We report the prenatal, pathological and genetic characteristics of a fetus with mosaic complete tetrasomy 21. This is the second well-documented description of a complete tetrasomy 21 in the literature. METHODS: Prenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21. RESULTS: Prenatal ultrasound examination revealed an isolated complete atrioventricular septal defect with normal karyotype on amniotic fluid. After termination of pregnancy, clinical examination of the fetus evoked trisomy 21 or Down syndrome. Chromosomal microarray analysis and FISH on lung tissue showed a mosaicism with four copies of chromosome 21 (tetrasomy 21). CONCLUSION: Our observation and the review of the literature reported the possibility of very weak mosaicism and disease-causing confined tissue-specific mosaicism in fetus or alive patients with chromosome 21 aneuploidy, mainly Down syndrome. In case of clinical diagnosis suggestive of Down syndrome, attention must be paid to the risk of false-negative test due to chromosomal mosaicism (very weak percentage, different tissue distribution). To overcome this risk, it is necessary to privilege the diagnostic techniques without culture step and to increase the number of cells and tissues analyzed, if possible. This study highlights the limits of microarray as the unique diagnostic approach in case of weak mosaic and French cytogenetics guidelines recommend to check anomalies seen in microarray by another technique on the same tissue.status: publishe

Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability

International audienc