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SIMPLE mutation analysis in dominant demyelinating Charcot‐Marie‐Tooth disease: three novel mutations
Author(s) -
Latour Philippe,
Gonnaud PierreMarie,
Ollag Elisabeth,
Chan Victor,
Perelman Serge,
Stojkovic Tanya,
Stoll Claude,
Vial Christophe,
Ziegler François,
Vandenberghe Antoon,
Maire Irène
Publication year - 2006
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2006.00080.x
Subject(s) - missense mutation , mutation , genetics , coding region , biology , tooth disease , gene , medicine
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).