Estimation of the size of the chromosome 17p11.2 duplication in Charcot-Marie-Tooth neuropathy type 1a (CMT1a). HMSN Collaborative Research Group.

Abstract

We have previously shown a duplication in 17p11.2 with probe pVAW409R3 (D17S122) in 12 families with hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1). In this study we aimed to estimate the size of the duplication using additional polymorphic DNA markers located in 17pll.2-p12. Two other 17pll.2 markers, pVAW412R3 (Dl7S125) and pEW401 (D17S61), were found to be duplicated in all HMSN I patients tested. Furthermore, all HMSN I patients showed the same duplication junction fragment with probe pVAW409R3. On the genetic map the duplicated markers span a minimal distance of 10 cM while on the physical map they are present in the same Nod restriction fragment of 1150 kb. The discrepancy between the genetic and physical map distances suggests that the 17pl1.2 region is extremely prone to recombinational events. The high recombination rate may be a contributing factor to the genetic instability of this chromosomal region.

Estimation of the Mutation Frequencies in Charcot-Marie-Tooth Disease Type 1 and Hereditary Neuropathy with Liability to Pressure Palsies: A European Collaborative Study

“…Subclones [39] of the following markers, free of repetitive se quences, were provided by the European CMT consortium group: pVAW409Rl, pVAW409R3, pVAW412R3, or pEW401. One or more of these markers, or the PMP22 probe pl32G8Rl [13], were used in the analysis.…”

Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases

“…Charcot-Marie-Tooth (CMT) diseases are a group of inherited neuropathies that affect motor and sensory nerves. A majority of CMT phenotypes can be classified as primary demyelination/dysmyelinating (CMT1) or primary axonal (CMT2) neuropathies.1,2 CMT type 1A (CMT1A z 80% of CMT1 cases 3,4 ) arises from duplication of the peripheral myelin protein 22 (PMP22) gene 5,6 and results in dysmyelination and secondary axonal loss. 7 CMT type 2A (CMT2A z 35% of CMT2 cases 8 ) is caused by missense mutations in the gene that encodes for mitofusin 2 9 and leads to primary axonal degeneration.…”

“…1,2 CMT type 1A (CMT1A z 80% of CMT1 cases 3,4 ) arises from duplication of the peripheral myelin protein 22 (PMP22) gene 5,6 and results in dysmyelination and secondary axonal loss. 7 CMT type 2A (CMT2A z 35% of CMT2 cases 8 ) is caused by missense mutations in the gene that encodes for mitofusin 2 9 and leads to primary axonal degeneration.…”

Fenótipos Raros de Neuropatia Hereditária: Charcot-Marie-Tooth Tipo 4

“…CMT4H em geral tem início precoce (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) Até o presente a doença só foi descrita nessa família francesa com descendência argelina.…”

“…A Tabela 1 salienta as principais características dos diversos subtipos de CMT. Em 1991, 2 grupos independentes demonstraram que CMT1A, a forma mais comum de CMT era causada por duplicação de 1.4 mB no gene que codifica a proteí-na PMP22 (cromossomo 17p11.2) 13,14 . Tal demonstração abriu uma nova era no estudo da CMT, com a identificação até o presente de pelo menos 47 genes diferentes 1 .…”