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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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Atlas_Id 10069
Genes implicated inBUB1B   CEP57  
  • 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
    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)


    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


    C-anaphases in lymphocyte cultures versus premature centromere division syndromes.
    Chamla Y
    Human genetics. 1988 ; 78 (2) : 111-114.
    PMID 3276615
    Mosaic variegated aneuploidies in a newborn with growth retardation and dismorphic phenotype.
    D'Agostino A, Calzone R, Poggi V, Zatterale A, Nitsch L
    C-anaphases: a mitotic variant.
    Domí MG, Rivera H
    Annales de genetique. 1992 ; 35 (3) : 183-185.
    PMID 1466571
    Premature centromere division dominantly inherited in a subfertile family.
    Gabarró J, Jimenez A, Glover G
    Cytogenetics and cell genetics. 1986 ; 43 (1-2) : 69-71.
    PMID 3780318
    Mosaic variegated aneuploidy with multiple congenital abnormalities: homozygosity for total premature chromatid separation trait.
    Kajii T, Kawai T, Takumi T, Misu H, Mabuchi O, Takahashi Y, Tachino M, Nihei F, Ikeuchi T
    American journal of medical genetics. 1998 ; 78 (3) : 245-249.
    PMID 9677059
    Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.
    Kawame H, Sugio Y, Fuyama Y, Hayashi Y, Suzuki H, Kurosawa K, Maekawa K
    Journal of human genetics. 1999 ; 44 (4) : 219-224.
    PMID 10429359
    Does ring syndrome exist? An analysis of 207 case reports on patients with a ring autosome.
    Kosztol´ G
    Human genetics. 1987 ; 75 (2) : 174-179.
    PMID 3817812
    Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma.
    Limwongse C, Schwartz S, Bocian M, Robin NH
    American journal of medical genetics. 1999 ; 82 (1) : 20-24.
    PMID 9916837
    Premature centromere division (PCD): a dominantly inherited cytogenetic anomaly.
    Madan K, Lindhout D, Palan A
    Human genetics. 1987 ; 77 (2) : 193-196.
    PMID 3653892
    Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint.
    Matsuura S, Ito E, Tauchi H, Komatsu K, Ikeuchi T, Kajii T
    American journal of human genetics. 2000 ; 67 (2) : 483-486.
    PMID 10877982
    Mitotic disturbance associated with mosaic aneuploidies.
    Miller K, Müller W, Winkler L, Hadam MR, Ehrich JH, Flatz SD
    Human genetics. 1990 ; 84 (4) : 361-364.
    PMID 2307459
    Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease.
    Plaja A, Vendrell T, Smeets D, Sarret E, Gili T, Català V, Mediano C, Scheres JM
    American journal of medical genetics. 2001 ; 98 (3) : 216-223.
    PMID 11169558
    A mitotic mutant causing non- disjunction in man.
    Scheres JM JC, Hustinx TWJ, Madam K, Beltman J D, Lindhout D
    In. : page 7.
    Mosaic variegated aneuploidy with microcephaly: a new human mitotic mutant?
    Warburton D, Anyane-Yeboa K, Taterka P, Yu CY, Olsen D
    Annales de genetique. 1991 ; 34 (3-4) : 287-292.
    PMID 1809239


    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 :

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes BUB1B

    External links

    OrphanetMosaic variegated aneuploidy syndrome
    Other database/diseases/3007/mosaic-variegated-aneuploidy-syndrome Mosaic variegated aneuploidy syndrome (GARD)
    Genes implicated inBUB1B   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inCEP57   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

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