Charcot-Marie-Tooth disease type 1 (CMT1) is a common disorder of the peripheral nervous system. The underlying genetic cause is highly heterogeneous, and mutations in SIMPLE (small integral membrane protein of lysosome/late endosome) represent a rare cause of CMT type 1, named CMT1C. Herein, we report the clinical, electrophysiological, and neuropathological findings of an Italian CMT1 family with a novel SIMPLE missense mutation. The family exhibited electrophysiological signs of demyelination, predominantly affecting the lower limbs, with conduction blocks, and a wide variability of age of onset among the members. Molecular analysis identified the novel heterozygous missense mutation p.Pro135Arg in SIMPLE which co-segregated with the disease within the pedigree. In conclusion, our findings confirm that the genetic analysis of LITAF/SIMPLE should be considered for the diagnostic flow-chart of CMT1 patient, especially when nerve conduction studies show the presence of conduction blocks.

Ciotti, P., Luigetti, M., Geroldi, A., Capponi, S., Pezzini, I., Gulli, R., Pazzaglia, C., Padua, L., Massa, R., Mandich, P., Bellone, E., A novel LITAF/SIMPLE mutation within a family with a demyelinating form of Charcot-Marie-Tooth disease, <<JOURNAL OF THE NEUROLOGICAL SCIENCES>>, 2014; 343 (1-2): 183-186. [doi:10.1016/j.jns.2014.05.029] [http://hdl.handle.net/10807/62477]

A novel LITAF/SIMPLE mutation within a family with a demyelinating form of Charcot-Marie-Tooth disease

Luigetti, Marco;Pazzaglia, Costanza;Padua, Luca;
2014

Abstract

Charcot-Marie-Tooth disease type 1 (CMT1) is a common disorder of the peripheral nervous system. The underlying genetic cause is highly heterogeneous, and mutations in SIMPLE (small integral membrane protein of lysosome/late endosome) represent a rare cause of CMT type 1, named CMT1C. Herein, we report the clinical, electrophysiological, and neuropathological findings of an Italian CMT1 family with a novel SIMPLE missense mutation. The family exhibited electrophysiological signs of demyelination, predominantly affecting the lower limbs, with conduction blocks, and a wide variability of age of onset among the members. Molecular analysis identified the novel heterozygous missense mutation p.Pro135Arg in SIMPLE which co-segregated with the disease within the pedigree. In conclusion, our findings confirm that the genetic analysis of LITAF/SIMPLE should be considered for the diagnostic flow-chart of CMT1 patient, especially when nerve conduction studies show the presence of conduction blocks.
2014
Inglese
Ciotti, P., Luigetti, M., Geroldi, A., Capponi, S., Pezzini, I., Gulli, R., Pazzaglia, C., Padua, L., Massa, R., Mandich, P., Bellone, E., A novel LITAF/SIMPLE mutation within a family with a demyelinating form of Charcot-Marie-Tooth disease, <<JOURNAL OF THE NEUROLOGICAL SCIENCES>>, 2014; 343 (1-2): 183-186. [doi:10.1016/j.jns.2014.05.029] [http://hdl.handle.net/10807/62477]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/62477
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