Acrocentric cryptic translocation associated with nondisjunction of chromosome 21.
Down syndrome is the most frequent autosome aneuploidy in live newborns. It was recently proposed that pericentromeric cryptic translocations might be a cause of chromosome nondisjunction. We describe here a phenotypically normal subject with a cryptic translocation involving the short arms of chromosomes 13 or 21 and 22, who had a son with Down syndrome. Fluorescent in situ hybridization (FISH) on paternal metaphase chromosomes showed a chromosome 22 centromere positive for both 13/21 and 14/22 centromeric probes. The same probes hybridized on different and contiguous sites of chromatin fibers, eliminating cross-hybridization artifacts. This confirmed the presence of a cryptic translocation generating a dicentric chromosome 22: fib ish dic(21;22)(21 pter --> 21q10::22q10 --> 22 qter)(D13/21Z1+;D14/22Z1+). Microsatellite STR segregation analysis confirmed the paternal origin of the additional chromosome 21 in the Down syndrome patient. To determine whether the father showed a higher-than-normal frequency of chromosome 21 nondisjunction, FISH analysis of spermatozoa was performed using a sequence specific probe (21q22.13-q22.2). The frequency of disomy 21 spermatozoa was twofold higher in the cryptic translocation carrier as compared to normal subjects (P < 0.014), suggesting that the rearrangement favored the nondisjunction of chromosome 21. This is the first report associating a pericentromeric cryptic translocation of acrocentric chromosomes with the generation of aneuploidy, supporting the hypothesis that this type of rearrangement may contribute to abnormal chromosomal segregation.
Ramos
Sandra
S
Laboratorio de Citogenética, Departamento de Investigación en Genética Humana, Instituto Nacional de Pediatría, México, Mexico.
Alcántara
Miguel Angel
MA
Molina
Bertha
B
del Castillo
Victoria
V
Sánchez
Silvia
S
Frias
Sara
S
D000782:Aneuploidy; D016022:Case-Control Studies; D002503:Centromere / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D015342:DNA Probes; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats; D009630:Nondisjunction, Genetic; D010375:Pedigree; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism
D015342:DNA Probes; D005819:Genetic Markers