Prenatal detection of a 17p11.2 duplication resulting from a rare recombination event and novel PCR-based strategy for molecular identification of Charcot-Marie-Tooth disease type 1A
R. Bernard et al., Prenatal detection of a 17p11.2 duplication resulting from a rare recombination event and novel PCR-based strategy for molecular identification of Charcot-Marie-Tooth disease type 1A, EUR J HUM G, 8(3), 2000, pp. 229-235
Charcot-Marie-Tooth disease, type 1A (CMT1A) is caused in most cases by a 1
.5 Mb duplication on chromosome 17p11.2 arising after unequal crossing-over
between repeated sequences called CMT1A-REPs, flanking the 1.5 Mb unit. A
3.2 kb recombination hot spot has been defined, resulting in a junction fra
gment between EcoRI (distal CMT1A-REP) and Sad (proximal CMT1A-REP). This w
as further reduced to a 1.7kb EcoRI-Nsil fragment, and recently to a 731 bp
hot spot region within this fragment. We describe the CMT1A-REPs-based PCR
method used to identify CMT1A duplications and report on a family case in
which a 29-year-old pregnant woman requested prenatal diagnosis for two suc
cessive pregnancies because her husband was affected with CMT1A. Our method
enabled us to characterise the duplication in both foetuses and demonstrat
e that it arose from a rare recombination event taking place outside the 1.
7 kb region. Since our approach is simple and enables the entire set of dup
lications occurring after recombination in the enlarged 3.2 kb region inclu
ding the hot spot to be detected, we suggest it might be considered for use
in primary screening for pre- and postnatal diagnosis of CMT1A.