title: A novel LITAF/SIMPLE mutation within a family with a demyelinating form of Charcot-Marie-Tooth disease.
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.
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy. Electronic address: paola.ciotti@unige.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Ciotti
authors.affiliation: Department of Geriatrics, Neurosciences & Orthopedics, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Luigetti
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Geroldi
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Capponi
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pezzini
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Gulli
authors.affiliation: Don Carlo Gnocchi Onlus Foundation, Milan, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Pazzaglia
authors.affiliation: Department of Geriatrics, Neurosciences & Orthopedics, Catholic University of Sacred Heart, Rome, Italy; Don Carlo Gnocchi Onlus Foundation, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Padua
authors.affiliation: Institute of Neurology, Tor Vergata University, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Massa
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Italy and UO Medical Genetics, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Bellone
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C118738:LITAF protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: CMT1 Italian patients; CMT1C; Conduction blocks; LITAF/SIMPLE; SIMPLE mutation; Sural nerve biopsy