Molecular diagnosis of Charcot-Marie-Tooth 1A disease and hereditary neuropathy with liability to pressure palsies by quantifying CMT1A-REP sequences: consequences of recombinations at variant sites on chromosomes 17p11.2-12.
The most frequent form of Charcot-Marie-Tooth disease (CMT1A; OMIM118.220) is the result of a duplication on chromosome 17 in pll.2-p12. This region contains PMP22, a gene expressed in peripheral myelin. The mutation results from an unequal crossing-over involving repeated sequences, CMT1A-REP, located on both sides of the duplicated region. The reciprocal product of this recombination is a deletion of the same region, which is associated with hereditary neuropathy with liability to pressure palsies (HNPP; OMIM162.500). Proximal and distal CMT1A-REP sequences can be distinguished by the presence of a variant EcoRI site. We quantified the number of these repeat sequences in 36 CMT1A and 40 HNPP patients. CMT1A-REP sequences are involved in almost all of the mutations. The majority of recombination breakpoints occur distally from the variant EcoRI site. However, a few have a breakpoint proximal to this site, which creates the risk of misinterpretation with respect to a duplicated/deleted status.
Vandenberghe
A
A
Neurogenetics Laboratory, University Claude Bernard, Faculty of Pharmacy, France.
Latour
P
P
Chauplannaz
G
G
Chapon
F
F
Pouget
J
J
Dumas
R
R
Laguenay
A
A
Ollagnon
E
E
Bost
M
M
Duthel
S
S
Chazot
G
G
Boucherat
M
M
D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000032:analysis*; D017353:Gene Deletion; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid
D004247:DNA