, Volume 14, Issue 2, pp 123–132 | Cite as

Dominant GDAP1 founder mutation is a common cause of axonal Charcot-Marie-Tooth disease in Finland

  • Mari Auranen
  • Emil Ylikallio
  • Jussi Toppila
  • Mirja Somer
  • Sari Kiuru-Enari
  • Henna Tyynismaa
Original Article


We describe a founder mutation in the gene encoding ganglioside-induced differentiation associated-protein 1 (GDAP1), leading to amino acid change p.H123R, as a common cause of autosomal dominant axonal Charcot-Marie-Tooth (CMT2) neuropathy in Finland. The mutation explains up to 14 % of CMT2 in Finland, where most patients with axonal neuropathy have remained without molecular diagnosis. Only three families out of 28 were found to carry putative disease mutations in the MFN2 gene encoding mitofusin 2. In addition, the MFN2 variant p.V705I was commonly found in our patients, but we provide evidence that this previously described mutation is a common polymorphism and not pathogenic. GDAP1-associated polyneuropathy caused predominantly a mild and slowly progressive phenotype. Besides distal leg muscle weakness, most patients showed mild proximal weakness, often with asymmetry and pes cavus. Our findings broaden the understanding of GDAP1 mutations in CMT2 phenotypes and provide support for the use of whole-exome sequencing in CMT gene diagnostics.


Charcot-Marie-Tooth disease Axonal neuropathy GDAP1 Founder mutation Exome sequencing 

Supplementary material

10048_2013_358_Fig5_ESM.jpg (62 kb)

Filtering steps of the exome data using the unbiased approach. From each of the families 1 and 2, two related CMT2 patients were subjected to exome sequencing. The number of variants for each filtering step are shown. The selected variants were the following: (1) Intragenic, (2) Heterozygous on autosomes, (3) Rare in the 1000Genomes project (<0.5 % frequency), (4) Nonsynonomous, (5) Predicted damaging by the SIFT Tool, (6) Shared by the two affected family members, (7) Not present in our in-house database of exome data from Finnish individuals (n = 50). (JPEG 61 kb)

10048_2013_358_MOESM1_ESM.tif (3.2 mb)
High-resolution image (TIFF 3,261 kb)
10048_2013_358_MOESM2_ESM.pdf (7 kb)
ESM 2(PDF 6 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mari Auranen
    • 1
    • 2
  • Emil Ylikallio
    • 1
  • Jussi Toppila
    • 3
  • Mirja Somer
    • 4
  • Sari Kiuru-Enari
    • 2
  • Henna Tyynismaa
    • 1
    • 5
  1. 1.Research Programs Unit, Molecular Neurology, Biomedicum-HelsinkiUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of NeurologyHelsinki University Central HospitalHelsinkiFinland
  3. 3.HUS Medical Imaging Center, Department of Clinical NeurophysiologyHelsinki University Central HospitalHelsinkiFinland
  4. 4.Department of Medical GeneticsVaestoliitto, The Family Federation of FinlandHelsinkiFinland
  5. 5.Department of Medical Genetics, Haartman InstituteUniversity of HelsinkiHelsinkiFinland

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