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Variegated aneuploidy related to premature centromere division (PCD)

Written2000-11Alberto Plaja
Unitat de Genötica, Hospital Materno- Infantil Vall d'Hebron Pg. Vall d'Hebron 119- 129, 08035- Barcelona, Spain

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Identity

Atlas_Id 10069
Genes implicated inBUB1B  CEP57  
Note
  • the term premature centromere division has also been utilized to describe an unrelated cytogenetic phenomenon, the age related loss of centromeric function in chromosome X
  • variegated aneuploidy has also been described in patients without PCD and patients with Roberts syndrome
  • Inheritance
  • only 11 patients known
  • premature centromere division (PCD) without variegated aneuploidy has been shown to have an autosomal dominant inheritance, with an estimated frequency of 0.1% of the population
  • it has been proposed that patients with variegated aneuploidy related to PCD are homozygotes for this trait, but in several cases one of the parents do not show elevated frequency of PCD
  • a recessive inheritance with hormonal factors modifying the expression of PCD in a carrier, isodisomy of one chromosome or loss of heterozygosity has been suggested
  • Clinics

    Note patients show a remarkably constant clinical phenotype probably due to high cellular mortality induced by the aneuploidies; similar clinical findings have also been found in other patients with an expected increased cellular mortality (variegated aneuploidy without PCD and the "ring syndrome")
    Phenotype and clinics the clinical phenotype of the 11 patients described in the literature includes microcephaly (11/11), central nervous system (CNS) anomalies (5/6) with cerebellar defects and migration defects, mental retardation (8/9), prenatal (always noted over 23 weeks of gestation) and postnatal growth retardation (10/10), flat and broad nasal bridge (4/7), apparently low-set ears (5/8), eye abnormalities (8/10), skin abnormalities (3/9) and ambiguous genitalia in male patients (4/6); seizures have been reported in 5 patients; cancer is a major concern in the clinical management of these patients (5/11); birth weight corrected for gestational age ranges from -1.3 to -4.1 SD, birth length from -0.8 to -5.4 SD and OFC from -2.6 to -5.8
    Neoplastic risk the occurrence of Wilms tumor in three patients, rhabdomyosarcoma in two others and acute leukemia in a fifth characterizes this condition as a chromosome instability disorder with a high risk of malignancy; interestingly enough, preferential loss of maternal 11p15.5 chromosome region has been repeatedly reported in Wilms tumor as well as in rhabdomyosarcoma
    Prognosis although published data is incomplete, at least 4 patients have died before 2 years of age, a fifth deceased at 42 years and one patient aged 18 month has an advanced, relapsed rhabdomyosarcoma; patient's death had been related to pneumonia (one patient), leukemia (one patient), and Wilms tumor (three cases)

    Cytogenetics

    Inborn conditions
  • the terms premature centromere division (PCD), C-anaphases, premature anaphase, premature chromatid separation and asynchrony of mitotic stages describe cells in division which have overcome a colchicine-induced metaphase block; the resulting mitotic configuration shows split centromeres and splayed chromatids in all or most of the chromosomes.
  • control individuals generally show low frequencies of PCD (up to 3% of the mitoses), which seems to have no pathological relevance, but in 0.1% of the population an elevated PCD frequency (>5%) is found in colchicine exposed lymphocyte cultures; this type of PCD shows autosomal dominant inheritance and has traditionally considered to be harmless with the possible exception of some patients with subfertility or repeated abortion.
  • in few patients high levels of PCD (25- 87%) are found in combination with an increased number of cells with mosaic aneuploidies, microcephaly, mental retardation and a variety of malformations; in these patients, trisomy is by far more frequent than monosomy; trisomies of chromosome 8, 18 and X predominate in lymphocyte cultures and trisomy 2, 7, 12 and 20 predominate in fibroblasts; usually, at least one of the parents shows an elevated PCD frequency (range 12.6-42.5) but not variegated aneuploidy.
  • high levels of PCD have been reported in skin fibroblasts (althought in at least one case no aneupoidies where found), hair-root, bone marrow and trophoblastic cells of chorionic villi; there is no data of PCD expression in amniocytes but pseudomosaicism of chromosome 7 and 21 has been reported in amniocytes; cord blood chromosome analysis in one case showed PCD and variegated aneuploidies.
  •  
      cell showing premature centromere division (PCD) phenomenon, with split centromeres and splayed chromatids in all the chromosomes
    Cytogenetics of cancer cytogenetic analysis of one embryonal rhabdosarcoma showed normal karyotype in cultured cells and extensive aneuploidy with some estructural aberrations in the only two cells obtained from direct harvest

    Bibliography

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    Citation

    This paper should be referenced as such :
    Plaja, A
    Variegated aneuploidy related to premature centromere division (PCD)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):69-71.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/VariegAneuplPCDID10069.html


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