title: Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.
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.
authors.affiliation: Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Sevilla
authors.forename: D
authors.initials: D
authors.lastname: Martínez-Rubio
authors.forename: C
authors.initials: C
authors.lastname: Márquez
authors.forename: C
authors.initials: C
authors.lastname: Paradas
authors.forename: J
authors.initials: J
authors.lastname: Colomer
authors.forename: T
authors.initials: T
authors.lastname: Jaijo
authors.forename: J M
authors.initials: JM
authors.lastname: Millán
authors.forename: F
authors.initials: F
authors.lastname: Palau
authors.forename: C
authors.initials: C
authors.lastname: Espinós
mesh_terms: D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005843:Geography; D006239:Haplotypes; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology; D006593:Hexokinase / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011506:Proteins / Q000235:genetics; D006178:Romani People / Q000235:genetics*; D013030:Spain; D055815:Young Adult; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D006593:Hexokinase; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C488620:SH3TC2 protein, human; C472074:HK1 protein, human