Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the recurrent constitutional t(11;22).
Palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11 at the constitutional t(11;22) breakpoint are predicted to induce genomic instability, which mediates the translocation. A PCR-based translocation-detection system for the t(11;22) has been developed with PCR primers flanking the PATRRs of both chromosomes, to examine the involvement of the PATRRs in the recurrent rearrangement. Forty unrelated carriers of the t(11;22) balanced translocation, plus two additional, independent cases with the supernumerary-der(22) syndrome, were analyzed to compare their translocation breakpoints. Similar translocation-specific junction fragments were obtained from both derivative chromosomes in all 40 carriers of the t(11;22) balanced translocation and from the der(22) in both of the offspring with unbalanced supernumerary-der(22) syndrome, suggesting that the breakpoints in all cases localize within these PATRRs and that the translocation is generated by a similar mechanism. This PCR strategy provides a convenient technique for rapid diagnosis of the translocation, indicating its utility for prenatal and preimplantation diagnosis in families including carriers of the balanced translocation.
Kurahashi
H
H
Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Shaikh
T H
TH
Zackai
E H
EH
Celle
L
L
Driscoll
D A
DA
Budarf
M L
ML
Emanuel
B S
BS
D019457:Chromosome Breakage / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D044469:Racial Groups / Q000235:genetics; D013997:Time Factors; D014178:Translocation, Genetic / Q000235:genetics*
D017931:DNA Primers