G2Cdb::Human Disease report

Disease id
D00000205
Name
Charcot-Marie-Tooth disease type 1A
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001806 PLP1
proteolipid protein 1
Y (8615087) Polymorphism (P) Y
G00001806 PLP1
proteolipid protein 1
Y (8615087) Duplication (Du) Y

References

  • Charcot-Marie-Tooth disease type 1A: morphological phenotype of the 17p duplication versus PMP22 point mutations.

    Gabreëls-Festen AA, Bolhuis PA, Hoogendijk JE, Valentijn LJ, Eshuis EJ and Gabreëls FJ

    Institute of Neurology, University Hospital Nijmegen, The Netherlands.

    Charcot-Marie-Tooth disease type 1A (CMT1A) or hereditary motor and sensory neuropathy type Ia (HMSN type Ia) is an autosomal dominant demyelinating polyneuropathy, which may result from duplications as large as 1.5 Mb on chromosome 17p 11.2-p12 encompassing the gene for the peripheral myelin protein PMP22, or from point mutations in this gene. In general, it is not possible to distinguish, by clinical and neurophysiological criteria, the cases associated with the duplication mutation from those associated with point mutations of the PMP22 gene, although the latter tend to be more severe. In this study we demonstrated that the two genotypes exhibit different morphological characteristics. In the PMP22 duplicated cases the mean g-ratio (axon diameter versus fibre diameter) is significantly lower than normal, while in cases of PMP22 point mutations nearly all myelinated fibers have an extremely high g-ratio. In cases with point mutations, onion bulbs are abundantly present from an early age, whereas onion bulbs in the duplicated cases develop gradually in the first years of life. Increase in total transverse fascicular area is most pronounced in the point mutation cases. The differences in pathology between these two very different types of mutations involving the same gene likely reflect differences in pathogenesis and may offer clues in understanding the function of PMP22.

    Acta neuropathologica 1995;90;6;645-9

Literature (1)

Pubmed - human_disease

  • Charcot-Marie-Tooth disease type 1A: morphological phenotype of the 17p duplication versus PMP22 point mutations.

    Gabreëls-Festen AA, Bolhuis PA, Hoogendijk JE, Valentijn LJ, Eshuis EJ and Gabreëls FJ

    Institute of Neurology, University Hospital Nijmegen, The Netherlands.

    Charcot-Marie-Tooth disease type 1A (CMT1A) or hereditary motor and sensory neuropathy type Ia (HMSN type Ia) is an autosomal dominant demyelinating polyneuropathy, which may result from duplications as large as 1.5 Mb on chromosome 17p 11.2-p12 encompassing the gene for the peripheral myelin protein PMP22, or from point mutations in this gene. In general, it is not possible to distinguish, by clinical and neurophysiological criteria, the cases associated with the duplication mutation from those associated with point mutations of the PMP22 gene, although the latter tend to be more severe. In this study we demonstrated that the two genotypes exhibit different morphological characteristics. In the PMP22 duplicated cases the mean g-ratio (axon diameter versus fibre diameter) is significantly lower than normal, while in cases of PMP22 point mutations nearly all myelinated fibers have an extremely high g-ratio. In cases with point mutations, onion bulbs are abundantly present from an early age, whereas onion bulbs in the duplicated cases develop gradually in the first years of life. Increase in total transverse fascicular area is most pronounced in the point mutation cases. The differences in pathology between these two very different types of mutations involving the same gene likely reflect differences in pathogenesis and may offer clues in understanding the function of PMP22.

    Acta neuropathologica 1995;90;6;645-9

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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