Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia

J Appl Genet. 2013 Nov;54(4):455-60. doi: 10.1007/s13353-013-0168-7. Epub 2013 Aug 31.


Autosomal recessive forms of Charcot-Marie-Tooth disease (CMT) account for less than 10 % of all CMT cases, but are more frequent in the populations with a high rate of consanguinity. Roma (Gypsies) are a transnational minority with an estimated population of 10 to 14 million, in which a high degree of consanguineous marriages is a generally known fact. Similar to the other genetically isolated founder populations, the Roma harbour a number of unique or rare autosomal recessive disorders, caused by "private" founder mutations. There are three subtypes of autosomal recessive CMT with mutations private to the Roma population: CMT4C, CMT4D and CMT4G. We report on the molecular examination of four families of Roma origin in Slovakia with early-onset demyelinating neuropathy and autosomal recessive inheritance. We detected mutation p.R148X (g.631C>T) in the NDRG1 (NM_006096.3) gene in two families and mutation g.9712G>C in the HK1 (NM_033498) gene in the other two families. These mutations cause CMT4D and CMT4G, respectively. The success of molecular genetic analysis in all families confirms that autosomal recessive forms of CMT caused by mutations on the NDRG1 and HK1 genes are common causes of inherited neuropathies among Slovak Roma. Providing genetic analysis of these genes for patients with Roma origin as a common part of diagnostic procedure would contribute to a better rate of diagnosed cases of demyelinating neuropathy in Slovakia and in other countries with a Roma minority.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Charcot-Marie-Tooth Disease / genetics
  • Consanguinity
  • Female
  • Founder Effect*
  • Genes, Recessive
  • Genetic Testing
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Heterozygote
  • Hexokinase / genetics*
  • Homozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mutation*
  • Pedigree
  • Refsum Disease / genetics
  • Roma / genetics
  • Sequence Analysis, DNA
  • Slovakia


  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • HK1 protein, human
  • Hexokinase

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 4C
  • Neuropathy, hereditary motor and sensory, LOM type
  • Neuropathy, hereditary motor and sensory, Russe type