TY - JOUR
T1 - The constitutional t(17;22)
T2 - Another translocation mediated by palindromic AT-rich repeats
AU - Kurahashi, Hiroki
AU - Shaikh, Tamim
AU - Takata, Masayuki
AU - Toda, Tatsushi
AU - Emanuel, Beverly S.
N1 - Funding Information:
The authors thank Dr. D. H. Ledbetter, for patient samples for this study; Sara Dutton Sackett, for laboratory assistance; and Dr. M. Taniguchi, for valuable discussions and careful review of the manuscript. These studies were supported in part by CA39926, DC02027, and HD26979 from the National Institutes of Health and by funds provided by the Charles E. H. Upham Chair in Pediatrics (to B.S.E.).. The studies were also supported, in part, by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (to H.K.).
PY - 2003/3/1
Y1 - 2003/3/1
N2 - We have demonstrated that the breakpoints of the constitutional t(11;22) are located at palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11. As a mechanism for this recurrent translocation, we proposed that the PATRR forms a cruciform structure that induces the genomic instability leading to the rearrangement. A patient with neurofibromatosis type 1 (NF1) had previously been found to have a constitutional t(17;22) disrupting the NF1 gene on 17q11. We have localized the breakpoint on 22q11 within the 22q11-specific low-copy repeat where the breakpoints of the constitutional t(11;22)s reside, implying a similar palindrome-mediated mechanism for generation of the t(17;22). The NF1 gene contains a 195-bp PATRR within intron 31. We have isolated the junction fragments from both the der(17) and the der(22). The breakpoint on 17q11 is close to the center of the PATRR. A published breakpoint of an additional NF1-afflicted patient with a constitutional t(17;22) is also located close to the center of the same PATRR. Our data lend additional support to the hypothesis that PATRR-mediated genomic instability can lead to a variety of translocations.
AB - We have demonstrated that the breakpoints of the constitutional t(11;22) are located at palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11. As a mechanism for this recurrent translocation, we proposed that the PATRR forms a cruciform structure that induces the genomic instability leading to the rearrangement. A patient with neurofibromatosis type 1 (NF1) had previously been found to have a constitutional t(17;22) disrupting the NF1 gene on 17q11. We have localized the breakpoint on 22q11 within the 22q11-specific low-copy repeat where the breakpoints of the constitutional t(11;22)s reside, implying a similar palindrome-mediated mechanism for generation of the t(17;22). The NF1 gene contains a 195-bp PATRR within intron 31. We have isolated the junction fragments from both the der(17) and the der(22). The breakpoint on 17q11 is close to the center of the PATRR. A published breakpoint of an additional NF1-afflicted patient with a constitutional t(17;22) is also located close to the center of the same PATRR. Our data lend additional support to the hypothesis that PATRR-mediated genomic instability can lead to a variety of translocations.
UR - https://www.scopus.com/pages/publications/0037371163
UR - https://www.scopus.com/pages/publications/0037371163#tab=citedBy
U2 - 10.1086/368062
DO - 10.1086/368062
M3 - Article
C2 - 12557125
AN - SCOPUS:0037371163
SN - 0002-9297
VL - 72
SP - 733
EP - 738
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -