Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA by extruding DNA loops. The dramatic change in morphology of chromosomal DNAs between interphase and mitosis is one of the defining features of the eukaryotic cell cycle. We compare the patients’ characteristics with a list of features from MCPH1 cases described in the literature, in an effort to provide additional clues for a comprehensive definition of disease presentation and evolution. Genetic testing detected a homozygous deletion of exons 1–8 of MCPH1. magnetic resonance imaging revealed ventriculomegaly, simplified gyral pattern in the frontal lobes, and a neuronal migration defect. Here, we present a novel patient with congenital microcephaly, ID, language delay, short stature, and other minor features such as strabismus. Despite numerous studies on MCPH1 function, MCPH1-affected individuals are rare and the available clinical reports are not sufficient to define the natural history of the disease. It is also involved in DNA damage response and telomere maintenance in the nucleus. The first causative gene identified, MCPH1 or Microcephalin, encodes a centrosomal protein that modulates chromosome condensation and cell cycle progression. The genetic etiology of MCPH is heterogeneous and comprises more than 20 loci, nearly all following a recessive inheritance pattern. Microcephaly primary hereditary (MCPH) is a congenital disease characterized by nonsyndromic reduction in brain size due to impaired neurogenesis, often associated with a variable degree of intellectual disability (ID). Only a minor fraction of the observed cells with the typical morphology of prophase cells contained nuclear signals for both Cyclin B and Histone H3-PS10 proteins. G1-PLCs are also negative for both markers. Note that G2-PLCs and real prophases are indistinguishable by DAPI staining but showed different IF patterns for both markers. PLCs ("Prophase-like cells") refers to cells with condensed chromatin inside a retained nuclear envelope, either as a consequence of premature onset of chromosome condensation or delayed decondensation at the end of mitosis. (d) Immunolocalization using antibodies against Cyclin B and Histone H3-PS10 proteins in proliferating cells from one MCPH1 patient. Data from two independent experiments are presented. (c) Rate of H3PS10 positive cells in control and MCPH1 patient cells, determined by FACS after incubation with nocodazole for the indicated time points. data from at least 3 independent experiments are shown. As expected, PLC frequency was negligible in control cells. More than 500 cells were scored per sample. We also included cells incubated with nocodazole for 7 hours in these analyses. (b) For each sample from A, we determined in parallel the fraction of PLCs (prophase-like cells) by microscopic analyses of cytogenetic preparations. (a) Graphs comparing the cell cycle distribution, determined by FACS analyses, in untreated cell samples or cell samples incubated with nocodazole for 4 hours to induce M arrest. Cell cycle progression and dynamics of prophase like-condensation in control and MCPH1 patient cells.
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