SIMPLE mutation analysis in dominant demyelinating Charcot-Marie-Tooth disease: three novel mutations.

Abstract

Charcot-Marie-Tooth disease type 1C (CMT1C) is caused by mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE). We analyzed the coding sequence of SIMPLE in DNA of 53 unrelated cases of dominant demyelinating CMT disease with no mutations in PMP22, GJB1, MPZ, EGR2, and NEFL genes. Four different missense mutations were observed in six families. The mutation Gly112Ser was found in two families confirming its frequent occurrence in SIMPLE mutations. Three novel mutations were also identified: Ala111Gly (two families), Pro135Ser, and Pro135Thr. Familial studies revealed that all carriers of mutations (n = 38), aged from 1 to 78 years, were symptomatic, notably children under 10 years (n = 8). Motor conduction velocities in the median nerve ranked from 16.4 to 32.8 m/s (n = 20). In our series of 968 unrelated dominant demyelinating CMT cases (1992-2005), the percentage of SIMPLE mutations was 0.6 (6/968).

• Authors: Philippe Latour, Pierre-Marie Gonnaud, Elisabeth Ollagnon, Victor Chan, Serge Perelman, Tanya Stojkovic, Claude Stoll, Christophe Vial, François Ziegler, Antoon Vandenberghe, Irène Maire
• Journal: Journal of the peripheral nervous system : JPNS (J Peripher Nerv Syst) Vol. 11 Issue 2 Pg. 148-55 (Jun 2006) ISSN: 1085-9489 [Print] United States
• PMID: 16787513 (Publication Type: Comparative Study, Journal Article)

Chemical References

• LITAF protein, human
• Nuclear Proteins
• Transcription Factors

Topics

• Adolescent
• Adult
• Aged
• Charcot-Marie-Tooth Disease (genetics, physiopathology)
• Child
• Child, Preschool
• DNA Mutational Analysis (methods)
• Exons (genetics)
• Family Health
• Female
• Genes, Dominant (genetics)
• Humans
• Infant
• Male
• Middle Aged
• Mutation
• Nuclear Proteins (analysis, genetics)
• Pedigree
• Phenotype
• Retrospective Studies
• Sequence Analysis, Protein
• Transcription Factors (genetics)