TY - JOUR
T1 - A novel LITAF/SIMPLE mutation within a family with a demyelinating form of Charcot-Marie-Tooth disease
AU - Ciotti, Paola
AU - Luigetti, Marco
AU - Geroldi, Alessandro
AU - Capponi, Simona
AU - Pezzini, Ilaria
AU - Gulli, Rossella
AU - Pazzaglia, Costanza
AU - Padua, Luca
AU - Massa, Roberto
AU - Mandich, Paola
AU - Bellone, Emilia
PY - 2014/8/15
Y1 - 2014/8/15
N2 - 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.
AB - 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.
KW - CMT1 Italian patients
KW - CMT1C
KW - Conduction blocks
KW - LITAF/SIMPLE
KW - SIMPLE mutation
KW - Sural nerve biopsy
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U2 - 10.1016/j.jns.2014.05.029
DO - 10.1016/j.jns.2014.05.029
M3 - Article
C2 - 24880540
AN - SCOPUS:84904245757
VL - 343
SP - 183
EP - 186
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -