title: 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.
abstract: 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.
authors.affiliation: Neurogenetics Laboratory, University Claude Bernard, Faculty of Pharmacy, France.
authors.forename: A
authors.initials: A
authors.lastname: Vandenberghe
authors.forename: P
authors.initials: P
authors.lastname: Latour
authors.forename: G
authors.initials: G
authors.lastname: Chauplannaz
authors.forename: F
authors.initials: F
authors.lastname: Chapon
authors.forename: J
authors.initials: J
authors.lastname: Pouget
authors.forename: R
authors.initials: R
authors.lastname: Dumas
authors.forename: A
authors.initials: A
authors.lastname: Laguenay
authors.forename: E
authors.initials: E
authors.lastname: Ollagnon
authors.forename: M
authors.initials: M
authors.lastname: Bost
authors.forename: S
authors.initials: S
authors.lastname: Duthel
authors.forename: G
authors.initials: G
authors.lastname: Chazot
authors.forename: M
authors.initials: M
authors.lastname: Boucherat
mesh_terms: 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
chemical_list: D004247:DNA