Genetics of the Charcot‐Marie‐Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy‐Russe in depth. (10th October 2012)

• Record Type: Journal Article
• Authors: Sevilla, T; Martínez‐Rubio, D; Márquez, C; Paradas, C; Colomer, J; Jaijo, T; Millán, JM; Palau, F; Espinós, C
• Is Part Of: Clinical genetics. Volume 83:Number 6(2013:Jun.)
• Page Start: 565
• Page End: 570
• Publication Date: 2012-10-10
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12015
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>NDRG1</italic> p.R148X in CMT type 4D (CMT4D/HMSN‐Lom); p.C737_P738delinsX and p.R1109X mutations in the <italic>SH3TC2</italic> gene (CMT4C); and a G&gt;C change in a novel alternative untranslated exon in the <italic>HK1</italic> 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 <italic>HK1</italic> g.9712G&gt;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.</p> </abstract>