Jg. Chang et al., RAPID DETECTION OF A RECOMBINANT HOTSPOT ASSOCIATED WITH CHARCOT-MARIE-TOOTH-DISEASE TYPE 1A DUPLICATION BY A PCR-BASED DNA TEST, Clinical chemistry, 44(2), 1998, pp. 270-274
A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) cau
sed by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is as
sociated with Charcot-Marie-Tooth disease type 1A (CMT1A). A hotspot o
f crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs a
ccounts for three-quarters of the rearrangements in CMT1A patients. We
developed a PCR-based diagnostic method to detect a recombination hot
spot associated with the CMT1A duplication. Thirty-one CMT1A Chinese p
atients from different families and 50 healthy people over 65 years of
age were studied, Twenty-seven of the 31 cases demonstrated the 3.2-k
b hotspot crossover, of which there were two subgroups. The type 1 cro
ssover breakpoint was located at the distal CMT1A-REP around the PmeI
site, and accounted for 24 of the 27 cases with a 3.2-kb hotspot cross
over in CMT1A duplication patients. The type 2 crossover breakpoint wa
s located at the distal CMT1A-REP around the base 3625 region, account
ing for 3 of the 27 cases. The results correlated very well with the r
esults of Southern transfer analysis. This study has a potentially imp
ortant role in the diagnosis of CMT1A disease.