The Experts below are selected from a list of 1092 Experts worldwide ranked by ideXlab platform
Gian Maria Fabrizi - One of the best experts on this subject based on the ideXlab platform.
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thr124met Myelin Protein Zero mutation mimicking motor neuron disease
Amyotrophic Lateral Sclerosis, 2021Co-Authors: Giulia Bisogni, Angela Romano, Amelia Conte, Giorgio Tasca, Daniela Bernardo, Marco Luigetti, Andrea Di Paolantonio, Gian Maria Fabrizi, Agata Katia Patanella, Emiliana MeleoAbstract:Mutations in Myelin Protein Zero (MPZ) are associated with heterogeneous manifestations. In this study, we report clinical, electrophysiological, pathological, and muscle MRI findings from two rela...
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the spectrum of charcot marie tooth disease due to Myelin Protein Zero an electrodiagnostic nerve ultrasound and histological study
Clinical Neurophysiology, 2018Co-Authors: Gian Maria Fabrizi, Federica Taioli, Tiziana Cavallaro, Ilaria Cabrini, Stefano Tamburin, Moreno Ferrarini, Francesca Magrinelli, Giampietro ZanetteAbstract:Abstract Objective Nerve ultrasound (US) data on Myelin Protein Zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology. Methods We recruited 36 patients (12 MPZ mutations), and correlated nerve US to clinical, electrodiagnostic measures, and sural nerve biopsy. Results According to motor nerve conduction velocity (MNCV) criteria, nine patients were categorized as “deMyelinating” CMT1B, 17 as “axonal” CMT2I/J, and 10 as dominant “intermediate” CMTDID. Sural nerve biopsy showed hypertrophic de-reMyelinating neuropathy with numerous complex onion bulbs in one patient, de-reMyelinating neuropathy with scanty/absent onion bulbs in three, axonal neuropathy in two, mixed deMyelinating-axonal neuropathy in five. Electrodiagnosis significantly differed in CMT1B vs. CMT2I/J and CMTDID subgroups. CMT1B had slightly enlarged nerve cross sectional area (CSA) especially at proximal upper-limb (UL) sites. CSA was negatively correlated to UL MNCV and not increased at entrapment sites. Major sural nerve pathological patterns were uncorrelated to UL nerve US and MNCV. Conclusions Sural nerve biopsy confirmed the wide pathological spectrum of MPZ-CMT. UL nerve US identified two major patterns corresponding to the CMT1B and CMT2I/J-CMTDID subgroups. Significance Nerve US phenotype of MPZ-CMT diverged from those in other deMyelinating peripheral neuropathies and may have diagnostic value.
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dejerine sottas syndrome with a silent nucleotide change of Myelin Protein Zero gene
Journal of The Peripheral Nervous System, 2011Co-Authors: Federica Taioli, Tiziana Cavallaro, Ilaria Cabrini, Alessandro Simonati, Silvia Testi, Gian Maria FabriziAbstract:Charcot-Marie-Tooth disease type 1B (CMT1B) and Dejerine-Sottas syndrome type B (DSSB) are caused by missense or frameshift mutations of Myelin Protein Zero (MPZ) gene. We identified an apparently silent synonymous c.411C>T transition in MPZ exon 3 (p.Gly137Gly) which segregated with DSS in a two-generation pedigree. Retro-transcriptional analysis of MPZ in the proband's archive sural nerve biopsy identified an r.410_448del mutant transcript which resulted from an activated cryptic splice site in exon 3 and led to an in-frame partial deletion of exon 3 (p.Gly137_Lys149del). Quantitative real-time polymerase chain reaction (QRT-PCR) compared with two unrelated CMT1B nerves carrying a frameshift c.306delA mutation (p.Asp104ThrfsX13) indicated that the r.410_448del was stable differing from the p.Asp104ThrfsX13-associated transcript which was subjected to nonsense-mediated decay. The report highlighted the possible pathogenic role of synonymous MPZ mutations and difficulties in interpreting results from routine mutational screenings.
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Myelin Protein Zero val102fs mutation manifesting with isolated spinal root hypertrophy
Neuromuscular Disorders, 2009Co-Authors: Corrado Marchini, Sandro Zambito Marsala, Matteo Bendini, Federica Taioli, Giuseppe Damante, Incoronata Renata Lonigro, Gian Maria FabriziAbstract:The Val102fs mutation of the Myelin Protein Zero gene (MPZ) has been associated with Charcot-Marie-Tooth disease type 1B (CMT1B). Here we describe an unusual presentation of the Val102fs mutation characterized by symptoms of spinal root hypertrophy with no overt peroneal muscular atrophy. Two sisters aged 41 and 35 years complained of neck pain and presented only pes cavus or deep-tendon hyporeflexia. In both of them magnetic resonance imaging revealed non-enhancing hypertrophy of spinal roots misdiagnosed as neurofibromatosis; neurophysiology disclosed a deMyelinating neuropathy and addressed the correct molecular diagnosis. This report adds new data concerning the clinical presentations of MPZ mutations.
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axonal neuropathy due to Myelin Protein Zero mutation misdiagnosed as amyloid neuropathy
Muscle & Nerve, 2008Co-Authors: Chiara Briani, Federica Taioli, Fausto Adami, Tiziana Cavallaro, Sergio Ferrari, Gian Maria FabriziAbstract:In up to 50% of chronic idiopathic axonal neuropathies, an underlying diagnosis may be identified, including hereditary neuropathy. Charcot-Marie-Tooth disease (CMT) is clinically and genetically heterogeneous. Several mutations in the Myelin Protein Zero (MPZ) gene have been associated with different CMT phenotypes, including classical deMyelinating CMT1B and the axonal form of the disease. Primary amyloidosis, a rare disease where the amyloid is formed by the N-terminal portion of a monoclonal immunoglobulin light chain, may be complicated by polyneuropathy. We report a patient who was incorrectly diagnosed with amyloid neuropathy, but was found to have axonal CMT1B only after sural nerve biopsy ruled out an acquired amyloid neuropathy.
M De Visser - One of the best experts on this subject based on the ideXlab platform.
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late onset axonal charcot marie tooth phenotype caused by a novel Myelin Protein Zero mutation
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: H M E Bienfait, Frank Baas, A A W M Gabreelsfesten, J H T M Koelman, Jessica E Hoogendijk, C G Faber, Jan J G M Verschuuren, J H J Wokke, M De VisserAbstract:A late onset axonal Charcot-Marie-Tooth phenotype is described, resulting from a novel mutation in the Myelin Protein Zero (MPZ) gene. Comparative computer modelling of the three dimensional structure of the MPZ Protein predicts that this mutation does not cause a significant structural change. The primary axonal disease process in these patients points to a function of MPZ in maintenance of the Myelinated axons, apart from securing stability of the Myelin layer.
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two amino acid substitutions in the Myelin Protein Zero gene of a case of charcot marie tooth disease associated with light near dissociation
Neuromuscular Disorders, 2002Co-Authors: H M E Bienfait, Frank Baas, A A W M Gabreelsfesten, J H T M Koelman, C T Langerhorst, M De VisserAbstract:Charcot-Marie-Tooth disease caused by mutations of the Myelin Protein Zero gene demonstrates considerable phenotypical variability. We describe a 45-year-old female with a peripheral neuropathy with deMyelinating and axonal features, pes cavus and pupillary light-near dissociation. She was heterozygous for two mutations in the Myelin Protein Zero gene (His81Tyr and Val113Phe), both present on the same allele. Our patient shows a less severe phenotype than previously described patients with a His81Arg mutation. Multiple mutations in the Myelin Protein Zero gene, as well as Charcot-Marie-Tooth with pupillary abnormalities have previously been described in rare instances. However, concurrent occurrence of both phenomena is a novel finding.
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clinically distinct codon 69 mutations in major Myelin Protein Zero in deMyelinating neuropathies
Annals of Neurology, 1996Co-Authors: P H S Meijerink, Frank Baas, A A W M Gabreelsfesten, M De Visser, Jessica E Hoogendijk, I Zorn, Henk Veldman, P A BolhuisAbstract:Mutations in the major peripheral Myelin Protein Zero (P0) gene on chromosome 1q21-q23 have been found with the hereditary deMyelinating polyneuropathy Charcot-Marie-Tooth type 1B. Here, we describe 2 patients with distinct neurological characteristics, carrying different substitutions at the same codon--Arg69His and Arg69Cys. The patients were heterozygous for the mutation, which in both appeared to be de novo. Histological examination of sural nerve biopsy specimens revealed defective Myelin as well as marked differences, confirming the importance of P0 in the compaction of Myelin.
Irena Hausmanowapetrusewicz - One of the best experts on this subject based on the ideXlab platform.
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dysMyelinating and deMyelinating charcot marie tooth disease associated with two Myelin Protein Zero gene mutations
Journal of Applied Genetics, 2011Co-Authors: Hanna Drac, Dagmara Kabzinska, Izabela Moszynska, Halina Strugalskacynowska, Irena Hausmanowapetrusewicz, Andrzej KochanskiAbstract:Mutations in the Myelin Protein Zero (MPZ) gene are the third most frequent cause of hereditary motor and sensory neuropathies (HMSN), also called Charcot–Marie–Tooth disorders (CMT). Only in case of recurrent mutations occurring in the MPZ gene is it possible to draw phenotype–genotype correlations essential for establishing the prognosis and outcomes of CMT1. We have surveyed a cohort of 67 Polish patients from CMT families with deMyelinating neuropathy for mutations in the MPZ gene. In this study, we report two CMT families in which the Ile135Thr and Pro132Leu mutations have been identified for the MPZ gene. These MPZ gene mutations had not been identified hitherto in the Polish population. The Pro132Leu mutation segregates with a severe early-onset dysMyelinating–hypoMyelinating neuropathy, whereas the Ile135Thr substitution is associated with the classical phenotype of CMT1. To the best of our knowledge, we present here, for the first time, morphological data obtained in two sural nerve biopsies pointing to a hypoMyelination–dysMyelination process in a family harboring the Pro132Leu mutation in the MPZ gene.
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early onset charcot marie tooth type 1b disease caused by a novel leu190fs mutation in the Myelin Protein Zero gene
European Journal of Paediatric Neurology, 2004Co-Authors: Andrzej Kochanski, Hanna Drac, Dagmara Kabzinska, Barbara Ryniewicz, Katarzyna Rowinskamarcinska, Irena HausmanowapetrusewiczAbstract:The spectrum of Charcot-Marie-Tooth (CMT) phenotypes segregating with mutations in the Myelin Protein Zero (MPZ) gene is wide and ranges from congenital hypoMyelinating neuropathy (CHN) through deMyelinating form of CMT to the axonal type of CMT disease. Within 94 MPZ gene mutations reported up to now, only a few were identified in the exon 4 of the MPZ gene. In this study we have identified a novel Leu190fs mutation in the MPZ gene. The Leu190fs mutation was found in a 14-year-old girl suffering from Charcot-Marie-Tooth type 1 disease (CMT1) with onset in early infancy. Similarly to the other MPZ gene frame-shift mutations reported as far the Leu190fs seems to have a dominant negative effect.
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focally folded Myelin in charcot marie tooth type 1b disease is associated with asn131lys mutation in Myelin Protein Zero gene short report
European Journal of Neurology, 2003Co-Authors: Andrzej Kochanski, Hanna Drac, H Jedrzejowska, Irena HausmanowapetrusewiczAbstract:Charcot-Marie-Tooth disease type 1B (CMT1B) is a deMyelinating neuropathy inherited as an autosomal dominant trait. The majority of CMT1B cases are caused by mutations in the Myelin Protein Zero (P0) gene (MPZ). Only a few mutations in MPZ gene have been reported to be associated with focally folded Myelin sheaths. We have studied five patients from one family with five generations, affected by CMT1B disease. The morphological studies of sural nerve biopsy performed in the proband revealed fibers with focally folded Myelin. DNA sequencing analysis showed the Asn131Lys mutation in the MPZ gene in three members of the affected family.
Frank Baas - One of the best experts on this subject based on the ideXlab platform.
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g p 88 peripheral neuropathies caused by mutations in the Myelin Protein Zero
Neuromuscular Disorders, 2012Co-Authors: G Salerno, Frank Baas, C Ortez, H Galvez, A Nascimento, J Campistol, C Jimenezmallebrera, J ColomerAbstract:Abstract Charcot–Marie–Tooth disease (CMT), is a group of clinically and genetically heterogeneous neuropathies divided into deMyelinating (CMT1) and axonal forms (CMT2). Mutations in the Myelin Protein Zero (MPZ/P0) gene are the third most frequent cause of CMT. This gene is a member of the immunoglobulin gene superfamily that encodes the most abundant Protein of the peripheral Myelin, necessary for Myelin compaction. There are many mutations in MPZ, most of them cause the CMT1B phenotype with normal early development but disability appears during the first two decades of life; and others, are responsible for severe neuropathies of infancy designated as Dejerine–Sottas syndrome. MPZ mutations have also been shown also in axonal type of CMT2. Hereby, we report the clinical and electrophysiological features of eight patients belonging to eight families affected by CMT 1B. The mean age of the patients is 13 years (range: 4–29). In five patients, the symptoms appeared between 2 and 3 years of age, showing motor clumsiness, difficulty to rise from the floor and for climbing stairs. In two cases, debuted before age of two, with a delay to develop an autonomous gait. The other one, presented an atypical phenotype at the age of seven, with hand tremor and episodes of muscular pain after exercising, with an intermittent increase of the CPK. Most of the patients had a stable evolution; five of them developed scoliosis and had affected their upper extremities. Only one of the patients developed a proximal weakness, and required scoliosis surgery at the age of 13. The electrophysiological study, showed a deMyelinating neuropathy in all of the cases. Two patients with the same mutation, C241A, had different clinical evolution. There is a wide clinical spectrum in patients with MPZ gene mutation, which makes difficult to establish a genotype-phenotype correlation. We recommend the study on MPZ gene in patients with deMyelinating neuropathy (once mutations in the PMP22 gene have been ruled out).
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late onset axonal charcot marie tooth phenotype caused by a novel Myelin Protein Zero mutation
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: H M E Bienfait, Frank Baas, A A W M Gabreelsfesten, J H T M Koelman, Jessica E Hoogendijk, C G Faber, Jan J G M Verschuuren, J H J Wokke, M De VisserAbstract:A late onset axonal Charcot-Marie-Tooth phenotype is described, resulting from a novel mutation in the Myelin Protein Zero (MPZ) gene. Comparative computer modelling of the three dimensional structure of the MPZ Protein predicts that this mutation does not cause a significant structural change. The primary axonal disease process in these patients points to a function of MPZ in maintenance of the Myelinated axons, apart from securing stability of the Myelin layer.
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two amino acid substitutions in the Myelin Protein Zero gene of a case of charcot marie tooth disease associated with light near dissociation
Neuromuscular Disorders, 2002Co-Authors: H M E Bienfait, Frank Baas, A A W M Gabreelsfesten, J H T M Koelman, C T Langerhorst, M De VisserAbstract:Charcot-Marie-Tooth disease caused by mutations of the Myelin Protein Zero gene demonstrates considerable phenotypical variability. We describe a 45-year-old female with a peripheral neuropathy with deMyelinating and axonal features, pes cavus and pupillary light-near dissociation. She was heterozygous for two mutations in the Myelin Protein Zero gene (His81Tyr and Val113Phe), both present on the same allele. Our patient shows a less severe phenotype than previously described patients with a His81Arg mutation. Multiple mutations in the Myelin Protein Zero gene, as well as Charcot-Marie-Tooth with pupillary abnormalities have previously been described in rare instances. However, concurrent occurrence of both phenomena is a novel finding.
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clinically distinct codon 69 mutations in major Myelin Protein Zero in deMyelinating neuropathies
Annals of Neurology, 1996Co-Authors: P H S Meijerink, Frank Baas, A A W M Gabreelsfesten, M De Visser, Jessica E Hoogendijk, I Zorn, Henk Veldman, P A BolhuisAbstract:Mutations in the major peripheral Myelin Protein Zero (P0) gene on chromosome 1q21-q23 have been found with the hereditary deMyelinating polyneuropathy Charcot-Marie-Tooth type 1B. Here, we describe 2 patients with distinct neurological characteristics, carrying different substitutions at the same codon--Arg69His and Arg69Cys. The patients were heterozygous for the mutation, which in both appeared to be de novo. Histological examination of sural nerve biopsy specimens revealed defective Myelin as well as marked differences, confirming the importance of P0 in the compaction of Myelin.
Federica Taioli - One of the best experts on this subject based on the ideXlab platform.
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the spectrum of charcot marie tooth disease due to Myelin Protein Zero an electrodiagnostic nerve ultrasound and histological study
Clinical Neurophysiology, 2018Co-Authors: Gian Maria Fabrizi, Federica Taioli, Tiziana Cavallaro, Ilaria Cabrini, Stefano Tamburin, Moreno Ferrarini, Francesca Magrinelli, Giampietro ZanetteAbstract:Abstract Objective Nerve ultrasound (US) data on Myelin Protein Zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology. Methods We recruited 36 patients (12 MPZ mutations), and correlated nerve US to clinical, electrodiagnostic measures, and sural nerve biopsy. Results According to motor nerve conduction velocity (MNCV) criteria, nine patients were categorized as “deMyelinating” CMT1B, 17 as “axonal” CMT2I/J, and 10 as dominant “intermediate” CMTDID. Sural nerve biopsy showed hypertrophic de-reMyelinating neuropathy with numerous complex onion bulbs in one patient, de-reMyelinating neuropathy with scanty/absent onion bulbs in three, axonal neuropathy in two, mixed deMyelinating-axonal neuropathy in five. Electrodiagnosis significantly differed in CMT1B vs. CMT2I/J and CMTDID subgroups. CMT1B had slightly enlarged nerve cross sectional area (CSA) especially at proximal upper-limb (UL) sites. CSA was negatively correlated to UL MNCV and not increased at entrapment sites. Major sural nerve pathological patterns were uncorrelated to UL nerve US and MNCV. Conclusions Sural nerve biopsy confirmed the wide pathological spectrum of MPZ-CMT. UL nerve US identified two major patterns corresponding to the CMT1B and CMT2I/J-CMTDID subgroups. Significance Nerve US phenotype of MPZ-CMT diverged from those in other deMyelinating peripheral neuropathies and may have diagnostic value.
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dejerine sottas syndrome with a silent nucleotide change of Myelin Protein Zero gene
Journal of The Peripheral Nervous System, 2011Co-Authors: Federica Taioli, Tiziana Cavallaro, Ilaria Cabrini, Alessandro Simonati, Silvia Testi, Gian Maria FabriziAbstract:Charcot-Marie-Tooth disease type 1B (CMT1B) and Dejerine-Sottas syndrome type B (DSSB) are caused by missense or frameshift mutations of Myelin Protein Zero (MPZ) gene. We identified an apparently silent synonymous c.411C>T transition in MPZ exon 3 (p.Gly137Gly) which segregated with DSS in a two-generation pedigree. Retro-transcriptional analysis of MPZ in the proband's archive sural nerve biopsy identified an r.410_448del mutant transcript which resulted from an activated cryptic splice site in exon 3 and led to an in-frame partial deletion of exon 3 (p.Gly137_Lys149del). Quantitative real-time polymerase chain reaction (QRT-PCR) compared with two unrelated CMT1B nerves carrying a frameshift c.306delA mutation (p.Asp104ThrfsX13) indicated that the r.410_448del was stable differing from the p.Asp104ThrfsX13-associated transcript which was subjected to nonsense-mediated decay. The report highlighted the possible pathogenic role of synonymous MPZ mutations and difficulties in interpreting results from routine mutational screenings.
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Myelin Protein Zero val102fs mutation manifesting with isolated spinal root hypertrophy
Neuromuscular Disorders, 2009Co-Authors: Corrado Marchini, Sandro Zambito Marsala, Matteo Bendini, Federica Taioli, Giuseppe Damante, Incoronata Renata Lonigro, Gian Maria FabriziAbstract:The Val102fs mutation of the Myelin Protein Zero gene (MPZ) has been associated with Charcot-Marie-Tooth disease type 1B (CMT1B). Here we describe an unusual presentation of the Val102fs mutation characterized by symptoms of spinal root hypertrophy with no overt peroneal muscular atrophy. Two sisters aged 41 and 35 years complained of neck pain and presented only pes cavus or deep-tendon hyporeflexia. In both of them magnetic resonance imaging revealed non-enhancing hypertrophy of spinal roots misdiagnosed as neurofibromatosis; neurophysiology disclosed a deMyelinating neuropathy and addressed the correct molecular diagnosis. This report adds new data concerning the clinical presentations of MPZ mutations.
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axonal neuropathy due to Myelin Protein Zero mutation misdiagnosed as amyloid neuropathy
Muscle & Nerve, 2008Co-Authors: Chiara Briani, Federica Taioli, Fausto Adami, Tiziana Cavallaro, Sergio Ferrari, Gian Maria FabriziAbstract:In up to 50% of chronic idiopathic axonal neuropathies, an underlying diagnosis may be identified, including hereditary neuropathy. Charcot-Marie-Tooth disease (CMT) is clinically and genetically heterogeneous. Several mutations in the Myelin Protein Zero (MPZ) gene have been associated with different CMT phenotypes, including classical deMyelinating CMT1B and the axonal form of the disease. Primary amyloidosis, a rare disease where the amyloid is formed by the N-terminal portion of a monoclonal immunoglobulin light chain, may be complicated by polyneuropathy. We report a patient who was incorrectly diagnosed with amyloid neuropathy, but was found to have axonal CMT1B only after sural nerve biopsy ruled out an acquired amyloid neuropathy.
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focally folded Myelin in charcot marie tooth neuropathy type 1b with ser49leu in the Myelin Protein Zero
Acta Neuropathologica, 2000Co-Authors: Gian Maria Fabrizi, Federica Taioli, Tiziana Cavallaro, Alessandro Simonati, F Rigatelli, G Mariani, P Perrone, Nicolo RizzutoAbstract:Charcot-Marie-Tooth disease type 1 B (CMT1B) is a deMyelinating neuropathy caused by mutations in the Myelin Protein Zero (P0) gene (MPZ). A few cases of CMT1B were recently found to be characterized by focally folded Myelin sheaths in nerve biopsy specimens; the significance of this association is unknown. Here, we describe two unrelated pedigrees harboring a heterozygous Ser49Leu substitution in P0ex. In both pedigrees, the mutation caused a late-onset, relatively mild CMT1B; in one pedigree, two patients had atrophy of peroneal muscles but hypertrophy of the gastrocnemius muscles. The sural nerve biopsy performed in the two index cases revealed an identical chronic deMyelinating and reMyelinating neuropathy dominated by focal foldings of the Myelin sheath shaped either as tomacula or as out/infoldings. The report adds Ser49Leu to the mutations of P0ex associated with focally folded Myelin and provides strong evidence that such a structural alteration of the Myelin sheath reflects a distinct pathogenetic mechanism in a subgroup of CMT1B.