Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach

Magdalena Zimoń, Esra Battaloğlu, Yesim Parman, Sevim Erdem, Jonathan Baets, Els De Vriendt, Derek Atkinson, Leonardo Almeida-Souza, Tine Deconinck, Burcak Ozes, Dirk Goossens, Sebahattin Cirak, Philip Van Damme, Mohammad Shboul, Thomas Voit, Lionel Van Maldergem, Bernard Dan, Mohammed S. El-Khateeb, Velina Guergueltcheva, Eduardo Lopez-LasoNathalie Goemans, Amira Masri, Stephan Züchner, Vincent Timmerman, Haluk Topaloğlu, Peter De Jonghe, Albena Jordanova

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Autosomal recessive forms of Charcot-Marie-Tooth disease (ARCMT) are rare but severe disorders of the peripheral nervous system. Their molecular basis is poorly understood due to the extensive genetic and clinical heterogeneity, posing considerable challenges for patients, physicians, and researchers. We report on the genetic findings from a systematic study of a large collection of 174 independent ARCMT families. Initial sequencing of the three most common ARCMT genes (ganglioside-induced differentiation protein 1—GDAP1, SH3 domain and tetratricopeptide repeats-containing protein 2—SH3TC2, histidine-triad nucleotide binding protein 1—HINT1) identified pathogenic mutations in 41 patients. Subsequently, 87 selected nuclear families underwent single nucleotide polymorphism (SNP) genotyping and homozygosity mapping, followed by targeted screening of known ARCMT genes. This strategy provided molecular diagnosis to 22 % of the families. Altogether, our unbiased genetic approach identified pathogenic mutations in ten ARCMT genes in a total of 41.3 % patients. Apart from a newly described founder mutation in GDAP1, the majority of variants constitute private molecular defects. Since the gene testing was independent of the clinical phenotype of the patients, we identified mutations in patients with unusual or additional clinical features, extending the phenotypic spectrum of the SH3TC2 gene. Our study provides an overview of the ARCMT genetic landscape and proposes guidelines for tackling the genetic heterogeneity of this group of hereditary neuropathies.

Original languageEnglish (US)
Pages (from-to)33-42
Number of pages10
Issue number1
StatePublished - Jan 2014


  • CMT
  • Charcot-Marie-Tooth disease
  • Homozygosity mapping
  • Inbred populations
  • Whole genome SNP genotyping

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach'. Together they form a unique fingerprint.

Cite this