title: Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group.
abstract: Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT 1) is an autosomal dominant disorder of the peripheral nervous system characterized by progressive weakness and atrophy of distal limb muscles. In the majority of HMSN I families, linkage studies localized the gene (CMT 1a) to the pericentromeric region of chromosome 17. We have detected with probe pVAW409R3 (D17S122) localized in 17p11.2 a duplication, co-segregating with the disease in 12 HMSN I families. In these families the duplication was present in all 128 patients but absent in the 84 unaffected and 44 married-in individuals (lod score of 58.44 at zero recombination). Further, on one HMSN I family the disease newly appeared simultaneously with a de novo duplication originating from an unequal crossing-over event at meiosis. Since different allelic combinations were found segregating with the duplication in different families linkage disequilibrium was not a significant factor. These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed.
authors.affiliation: Born-Bunge Foundation, Department of Biochemistry, University of Antwerp (UIA), Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Raeymaekers
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
authors.forename: E
authors.initials: E
authors.lastname: Nelis
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: J E
authors.initials: JE
authors.lastname: Hoogendijk
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: D F
authors.initials: DF
authors.lastname: Barker
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: De Visser
authors.forename: P A
authors.initials: PA
authors.lastname: Bolhuis
mesh_terms: D001345:Autoradiography; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000737:chemistry; D015342:DNA Probes; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D004247:DNA