Understanding the mechanism(s) of mosaic trisomy 21 by using DNA polymorphism analysis

Constantinos Pangalos, Dimitrios Avramopoulos, Jean Louis Blouin, Odile Raoul, Marie Christine DeBlois, Marguerite Prieur, Albert A. Schinzel, Maria Gika, Danae Abazis, Stylianos E. Antonarakis

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58 Scopus citations


In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, we genotyped 17 families with mosaic trisomy 21 probands, using 28 PCR- detectable DNA polymorphic markers that map in the pericentromeric region and long arm of chromosome 21. The percentage of cells with trisomy 21 in the probands' blood lymphocytes was 6%-94%. There were two classes of autoradiographic results: In class I, a 'third allele' lower intensity was detected in the proband's DNA for at least two chromosome 21 markers. The interpretation of this result was that the proband had inherited three chromosomes 21 after meiotic nondisjunction (NDJ) (trisomy 21 zygote) and subsequently lost one because of mitotic (somatic) error, the lost chromosome 21 being that with the lowest-intensity polymorphic allele. The parental origin and the meiotic stage of NDJ could also be determined. In class II, a 'third allele' was never detected. In these cases, the mosaicism probably occurred either by a postzygotic, mitotic error in a normal zygote that followed a normal meiosis (class IIA mechanism); by premeiotic, mitotic NDJ yielding an aneusomic zygote after meiosis, and subsequent mitotic loss (class IIB mechanism); or by a meiosis II error with lack of crossover in the preceding meiosis I, followed by mitotic loss after fertilization (class IIC mechanism). Among class II mechanisms, the most likely is mechanism IIA, while IIC is the least likely. There were 10 cases of class I and 7 cases of class II results. Within class I, there were nine cases with maternal meiotic errors (six meiosis I and three meiosis II errors, on the basis of pericentromeric markers) and one with paternal meiosis I error. The postzygotic loss of chromosome 21 was determined in eight maternal class I cases, and it was maternally derived in five cases and paternally derived in three; this suggests that the postzygotic loss of chromosome 21 is probably random. The mean maternal age in meiotic class I errors was 31.4 years and in mitotic class II errors was 27.4 years, as expected.

Original languageEnglish (US)
Pages (from-to)473-481
Number of pages9
JournalAmerican journal of human genetics
Issue number3
StatePublished - 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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