title: The frequency of 17p11.2 duplication and Connexin 32 mutations in 282 Charcot-Marie-Tooth families in relation to the mode of inheritance and motor nerve conduction velocity.
abstract: The 17p11.2 duplication and Connexin 32 (Cx32) mutations are the most frequent gene mutations responsible for Charcot-Marie-Tooth diseases. We classified 282 Charcot-Marie-Tooth families according to the median motor nerve conduction velocity of the index patient and the mode of inheritance, and screened them for 17p11.2 duplication and Cx32 mutations. Forty-seven percent of the Charcot-Marie-Tooth families had median motor nerve conduction velocity under 30 m/s (group 1), 15% between 30 and 40 m/s (group 2), and 28% over 40 m/s (group 3). Spinal Charcot-Marie-Tooth (group 4) was observed in 7% of the families. Modes of inheritance were not similarly represented among the different groups. The 17p11.2 duplication was detected in index patients of group 1 only, and accounted for 83% of the familial cases and 36% of the isolated cases. In contrast, 21 Cx32 mutations were detected to variable degrees in groups 1-3, but were most numerous by far in dominant families of group 2 (44%). This systematic approach was taken to estimate the frequency of 17p11.2 duplication and Cx32 mutations in the different Charcot-Marie-Tooth subgroups, in order to propose a practical strategy for molecular analysis.
authors.affiliation: Inserm U289, Hôpital de la Salpêtrière, 47 Boulevard de l'hôpital, 75651 Cedex 13, Paris, France. dubourg@ccr.jussieu.fr
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: S
authors.initials: S
authors.lastname: Tardieu
authors.forename: N
authors.initials: N
authors.lastname: Birouk
authors.forename: R
authors.initials: R
authors.lastname: Gouider
authors.forename: J M
authors.initials: JM
authors.lastname: Léger
authors.forename: T
authors.initials: T
authors.lastname: Maisonobe
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: P
authors.initials: P
authors.lastname: Bouche
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002886:Chromosomes, Human, Pair 17; D017630:Connexins / Q000235:genetics*; D005192:Family Health; D005260:Female; D020131:Genes, Duplicate; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009431:Neural Conduction; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein