Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.

Autores de IIS La Fe

• 

  Teresa Sevilla Mantecón

  Autor

• Celedonio Marquez Infante

  Autor

• Carmen Paradas Lopez

  Autor

• Teresa Jaijo Sanchís

  Autor

• 

  José María Millán Salvador

  Autor

• Francesc Palau Martinez

  Autor

• Carmen Espinos Armero

  Autor

Participantes ajenos a IIS La Fe

• Martínez-Rubio D
• Colomer J

Grupos

• Biomedicina Molecular, Celular y Genómica

  

  Leader

  José María Millán Salvador

• Patología Neuromuscular y Ataxias

  

  Investigador Principal

  Teresa Sevilla Mantecón

Abstract

Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1 gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to investigate in depth the genetics and the associated clinical symptoms of this CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1 g.9712G>C is a founder mutation, which arrived in Spain around the end of the 18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder leading to severe weakness of the lower limbs and prominent distal sensory loss. Motor nerve conduction velocity was in the demyelinating or intermediate range.