CMT 1C: SIMPLE mutation analysis in dominant demyelinating CMT: 3 novel mutation

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J Peripher Nerv Syst. 2006 Jun;11(2):148-55.

SIMPLE mutation analysis in dominant demyelinating Charcot-Marie-

Tooth disease: three novel mutations.

Latour P, Gonnaud PM, Ollagnon E, Chan V, Perelman S, Stojkovic T,

Stoll C, Vial C, Ziegler F, Vandenberghe A, Maire I.

Neurogenetique, Laboratoire de Biochimie Pediatrique, Hopital

Debrousse, Lyon, France.

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).