RESUMO
OBJECTIVE: Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). We aimed to investigate the frequency of disease-causing heterozygous GDAP1 mutations in ADCMT and their associated phenotype. METHODS: We performed mutation analysis in a large cohort of ADCMT patients by means of bidirectional sequencing of coding regions and exon-intron boundaries of GDAP1. Intragenic GDAP1 deletions were excluded using an allele quantification assay. We confirmed the pathogenic character of one sequence variant by in vitro experiments assaying mitochondrial morphology and function. RESULTS: In 8 Charcot-Marie-Tooth disease (CMT) families we identified 4 pathogenic heterozygous GDAP1 mutations, 3 of which are novel. Three of the mutations displayed reduced disease penetrance. Disease onset in the affected individuals was variable, ranging from early childhood to adulthood. Disease progression was slow in most patients and overall severity milder than typically seen in autosomal recessive GDAP1 mutations. Electrophysiologic changes are heterogeneous but compatible with axonal neuropathy in the majority of patients. CONCLUSIONS: With this study, we broaden the phenotypic and genetic spectrum of autosomal dominant GDAP1-associated neuropathies. We show that patients with dominant GDAP1 mutations may display clear axonal CMT, but may also have only minimal clinical and electrophysiologic abnormalities. We demonstrate that cell-based functional assays can be reliably used to test the pathogenicity of unknown variants. We discuss the implications of phenotypic variability and the reduced penetrance of autosomal dominant GDAP1 mutations for CMT diagnostic testing and counseling.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteínas do Tecido Nervoso/genética , Animais , Axônios/patologia , Células COS , Chlorocebus aethiops , Estudos de Coortes , Análise Mutacional de DNA , Éxons/genética , Genes Dominantes , Haplótipos , Células HeLa , Humanos , Íntrons/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mutação , Paternidade , Linhagem , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Among 57 mutations in the peripheral myelin protein 22 gene (PMP22) identified so far in patients affected by Charcot-Marie-Tooth disease (CMT), only 8 have been shown to segregate with a mixed phenotype of CMT and hearing impairment. In this study, we report a new Ser112Arg mutation in the PMP22 gene, identified in a patient with early-onset CMT and slowly progressive hearing impairment beginning in the second decade of life. We suggest that the Ser112Arg mutation in the PMP22 gene might have a causative role in the early-onset CMT with hearing impairment. Thus, our study extends the spectrum of CMT phenotypes putatively associated with PMP22 gene mutations.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Transtornos da Audição/genética , Proteínas da Mielina/genética , Adolescente , Adulto , Idade de Início , Envelhecimento/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Arginina/metabolismo , Audiometria , Doença de Charcot-Marie-Tooth/complicações , Criança , Pré-Escolar , Sequência Conservada , Transtornos da Audição/complicações , Humanos , Masculino , Dados de Sequência Molecular , Fenótipo , Serina/genéticaRESUMO
The pathogenesis of dilated cardiomyopathy in Emery- Dreifuss muscular dystrophy (EDMD) is still unknown. Autoimmune mechanisms have recently been taken into account. The aim of this investigation was to determine whether the level of circulating antibodies to heart proteins which were previously detected, correlates with disease progression. Troponin I was chosen as the target. Ten patients with EDMD and 10 age-matched normal controls were tested. An enzyme linked immunoassay (ELISA) technique was used to determine the possible relation between the level of anti-troponin I antibodies at diagnosis and at followup. Autoantibodies against troponin I were detected in all EDMD patients. At diagnosis the level was higher in the X-linked EDMD form (X-EDMD), as compared to the autosomal dominant form (AD-EDMD). At follow-up the elevated level of the autoantibodies persisted in all the EDMD cases. However, in the AD-EDMD form, the level was found to be significantly rising with disease progression, in the X-EDMD form, on the other hand, it was declining. No clear-cut relationship between the level of the circulating antibodies and cardiac symptomatology was present. Detection of anti-troponin I antibodies may provide a non-invasive marker of early stages of dilated cardiomyopathy in EDMD.
Assuntos
Autoanticorpos/sangue , Cardiomiopatia Dilatada/sangue , Distrofia Muscular de Emery-Dreifuss/imunologia , Troponina I/imunologia , Cardiomiopatia Dilatada/genética , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Humanos , MasculinoRESUMO
In recent years, 13 loci and 10 genes have been identified in Charcot-Marie-Tooth disorders with a recessive mode of inheritance (AR-CMT). Accordingly, the entity of AR-CMT has been divided into subgroups on the basis of genetic linkage. Mutations in the MTMR2, MTMR13, GDAP1, PRX, CTDPI, KIAA1985 and NDRG1 genes have been shown to be associated with specific CMT phenotypes. In AR-CMT disorders associated with mutations in the LMNA and MED25 genes the number of patients is still too low to achieve reliable phenotype-genotype correlations. In the present review, we summarize molecular, electrophysiological, neuropathological and clinical aspects of AR-CMT disorders.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Genes Recessivos , Doença de Charcot-Marie-Tooth/patologia , HumanosRESUMO
Motor unit (MU) potentials were recorded from brachial biceps of healthy subjects aged 5.5-79 years. The subjects were subdivided into young (5.5-19 year) and adult (37.5-79 year) groups, between which single MU discharge characteristics were compared. Firing rates were in the ranges of 8.3-21.7 s(-1) (mean 12.87 s(-1)) and 5.9-18.7 s(-1) (mean 11.08 s(-1)) for young and adult groups, respectively. Standard deviations (s.d.) of interspike intervals (ISIs) were in the range 4.84-11.57 ms (mean 8.39 ms) for the young group and 4.26-12.23 ms (mean 7.76 ms) for the adult group. Both differences were statistically significant (P < 0.001). Special attention was paid to the previously developed method of ISI variability analysis, which enabled the comparison of MUs with respect to afterhyperpolarization (AHP) duration of their motoneurones (MNs). The results show that AHP duration increases gradually with increasing age, which is in line with the transformation of muscle properties towards a slower phenotype. This transformation seems to be a continuous process, covering the entire lifespan of a human being, from childhood to senescence. The results presented here are significant for their insight into the ageing process of the neuromuscular system. The age-related change in AHP duration has not been investigated previously in human studies and has been met with ambiguous results in animal studies.
Assuntos
Potenciais de Ação/fisiologia , Envelhecimento/fisiologia , Neurônios Motores/fisiologia , Músculo Esquelético/inervação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular , Músculo Esquelético/fisiologiaRESUMO
This paper is a part of an introduction to authors' study on systemic laminopathies and their role in human aging. Of special interest is progeria--a type of systemic laminopathy associated usually with mutation 1824 C > T and presenting phenotype of preliminary aging. The authors analyse the differences between the progeria and other syndrome of preliminary aging--Werner's syndrome.
Assuntos
Envelhecimento , Progéria/fisiopatologia , Humanos , Modelos Biológicos , Prognóstico , Fatores de Risco , Síndrome de Werner/fisiopatologiaRESUMO
Charcot-Marie-Tooth type 4C4 disease (CMT4C4) is an early onset, autosomal recessive neuropathy with hoarseness caused by mutations in the GDAP1 gene which maps to the 8q13 region. To date, only 24 mutations in the GDAP1 gene have been reported. Neuropathological findings of sural nerve biopsies have been published for a limited number of CMT4C4 patients. Herein, a novel Pro153Leu mutation in the GDAP1 gene identified in a consanguineous Polish family is described and longitudinal clinical and electrophysiological studies as well as morphological findings are presented.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Mutação , Proteínas do Tecido Nervoso/genética , Adulto , Sequência de Aminoácidos , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/patologia , GTP Fosfo-Hidrolases/genética , Genótipo , Humanos , Leucina , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Transporte da Membrana Mitocondrial , Proteínas Mitocondriais/genética , Dados de Sequência Molecular , Atrofia Muscular , Fenótipo , Polônia , ProlinaRESUMO
Mutations in the ganglioside -induced differentiation-associated protein 1 (GDAP1) gene are common a cause of the Charcot-Marie-Tooth (CMT4A) disease with autosomal recessive mode of inheritance. To date more than twenty mutations in the GDAP1 gene have been reported in patients suffering from the demyelinating, axonal or mixed form of Charcot-Marie-Tooth disease. Only in a few CMT4A affected patients sural nerve biopsy findings have been provided. We report a homozygous Leu239Phe mutation in the GDAP1 gene in a 39-year-old female with a severe form of mixed axonal and demyelinating Charcot-Marie-Tooth disease.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteínas do Tecido Nervoso/genética , Adulto , Idade de Início , Doença de Charcot-Marie-Tooth/patologia , Pré-Escolar , Feminino , HumanosRESUMO
Charcot-Marie-Tooth type 4F disease (CMT4F) is an autosomal recessive neuropathy caused by mutations in the PRX gene. To date, only seven mutations have been identified in the PRX gene. In this study, the authors report a novel S399fsX410 mutation in the PRX gene and its effects at the protein level, which was identified in an 8-year-old patient with early-onset CMT disease.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteínas de Membrana/genética , Deleção de Sequência , Idade de Início , Doença de Charcot-Marie-Tooth/patologia , Criança , Éxons , Triagem de Portadores Genéticos , Humanos , Masculino , Nervo Sural/patologiaRESUMO
Dilated cardiomyopathy is one of the leading abnormalities in Emery-Dreifuss Muscular Dystrophy (EDMD). The pathogenesis of heart involvement in EDMD is, however, unknown. Autoimmune mechanisms have also to be taken into account. The aim of this study was to search for the presence of anti-heart antibodies in EDMD patients. The anti-heart auto-antibodies were detected in serum of 14 EDMD patients (the X-linked and the AD-Autosomal Dominant form). The control groups comprised 10 patients with Dilated Cardiomyopathy (DCM) and 10 healthy subjects. To screen serum for anti-heart antibodies against ventricular muscle proteins, they were separated by polyacrylamide gel electrophoresis, followed by Western blotting. In EDMD and DCM, IgG anti-heart antibodies against heart ventricular proteins were detected. In both diseases, 85 kD protein appeared to be the most immunogenic. Anti-troponin I (24 kD), anti-tropomyosin (35 kD) and anti-actin (43 kD) reactivity was less intense. There were significant differences in the reactivity of auto-antibodies between both EDMD forms, and also between EDMD and the DCM patients. No clear-cut correlation between the reactivity and frequency of the antibodies and clinical parameters of the EDMD patients was detected. The anti-heart proteins are reliable markers of immune involvement in dilated cardiomyopathy in the course of EDMD. Short- and long-term follow-up may define the role of anti-heart antibodies in predicting the susceptibility at risk of dilated cardiomyopathy in EDMD patients.
Assuntos
Autoanticorpos/sangue , Autoimunidade , Proteínas Musculares/imunologia , Distrofia Muscular de Emery-Dreifuss/sangue , Distrofia Muscular de Emery-Dreifuss/imunologia , Miocárdio/imunologia , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The aim of the study was to analyse electromyographic changes in Emery-Dreifuss muscular dystrophy (EDMD) that are atypical for myopathy. Our special interest was focused on high amplitude polyphasic motor unit potentials (MUPs), also termed irregular MUPs. METHODS: We studied 21 EDMD patients with the diagnosis based on clinical data, DNA analysis and immunohistochemical muscle studies. Rectus femoris muscle biopsies were investigated in all affected patients. Electrophysiological investigations involved quantitative concentric needle electromyography (CNEMG) of biceps brachii (BB) and rectus femoris (RF) muscles. Simulation studies were performed to approximate the number, diameter and distribution of muscle fibers, which contribute to irregular MUPs. RESULTS: The EMG data in EDMD were compatible with myopathy. Irregular MUPs showed longer duration, larger area, size index and higher amplitude then simple ones (P < 0.05). The approximation of features of muscle fibers contributing to irregular MUP also indicated smaller (<45 microm) and larger (>55 microm) diameters than normal (50 +/- 5 microm). Muscle biopsy specimens revealed the variable muscle fiber size due to atrophy, hypertrophy, and muscle fiber splitting. CONCLUSIONS: Irregular MUPs recorded in EDMD are due to hypertrophied and atrophied fibers as well as increased fiber density. They reflect reorganization of the motor unit in a slow progression myopathic process (muscle fiber hypertrophy and splitting). SIGNIFICANCE: Irregular MUPs in EDMD most probably reflect increased variability of the muscle fiber size.
Assuntos
Músculo Esquelético/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Adolescente , Adulto , Braço , Criança , Eletromiografia , Eletrofisiologia , Feminino , Humanos , Hipertrofia , Perna (Membro) , Masculino , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/patologiaRESUMO
A recessive demyelinating subtype of Charcot-Marie-Tooth disease called CMT4 is a heterogeneous group of disorders. A relatively frequent form of recessive CMT (CMT4 A) has been mapped to the chromosome 8 q21 and shown to be caused by mutations in the ganglioside-induced differentiation protein 1 (GDAP1) gene. Twenty mutations in the GDAP1 gene have been reported in patients suffering from the axonal and demyelinating forms of CMT disease. In this study we report two novel mutations in the GDAP1 gene in a patient suffering from CMT2 disease and whose parents were asymptomatic carriers of a Ser130Cys and 3'-splice site (311-1G > A) mutation, respectively.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Sítios de Splice de RNA/genética , Doença de Charcot-Marie-Tooth/patologia , Doença de Charcot-Marie-Tooth/fisiopatologia , Criança , Humanos , Masculino , Nervo Mediano/patologia , Nervo Mediano/fisiopatologia , Condução Nervosa/fisiologia , Nervo Fibular/patologia , Nervo Fibular/fisiopatologia , Nervo Sural/patologia , Nervo Sural/fisiopatologiaRESUMO
BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) characterized by musculoskeletal abnormalities is often associated with atrioventricular conduction disturbances. Although some EDMD patients were reported to develop dilated cardiomyopathy, there are limited data on their left ventricular (LV) performance. METHODS: Therefore, we echocardiographically assessed 27 men (23 cases aged 26.4+/-6.8 years with X-linked, and four cases aged 22.2+/-8.6 years with autosomal dominant (AD)) EDMD. Control group included 16 male healthy controls aged 24.8+/-6.0 (18-37) years. RESULTS: Although LV end diastolic dimension was similar in EDMD and controls (4.9+/-0.6 and 4.99+/-1.1 cm, ns), dilated left ventricle was found in three X-linked EDMD subjects. LV ejection fraction was significantly reduced in EDMD (62.3+/-1% vs. 71.2+/-2%, p=0.01) and was below 50% in six (22.2%) X-linked EDMD patients. Doppler analysis disclosed prolonged isovolumetric relaxation time of the left ventricle in the studied group. This finding may indicate impaired LV relaxation. CONCLUSION: A significant subgroup of X-linked EDMD patients shows pronounced abnormalities of left ventricular function. This warrants cardiologic follow up of EDMD patients.
Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia Doppler , Ventrículos do Coração/diagnóstico por imagem , Distrofia Muscular de Emery-Dreifuss/complicações , Função Ventricular Esquerda/fisiologia , Adolescente , Adulto , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/fisiopatologia , Cromossomos Humanos X/genética , Progressão da Doença , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Distrofia Muscular de Emery-Dreifuss/genética , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologiaRESUMO
Autosomal dominant axonal Charcot-Marie-Tooth disease type 2 (CMT2) is a heterogeneous group of disorders with seven chromosomal loci mapped in the uncomplicated forms of CMT2. The authors report clinical, electrophysiologic, and genetic analysis of a Polish CMT2 family. Nine known CMT2 gene loci and one MPZ gene locus have been excluded. The authors' findings suggest that this family represents a novel form of CMT2 disease.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Heterogeneidade Genética , Potenciais de Ação , Adolescente , Idade de Início , Axônios/patologia , Doença de Charcot-Marie-Tooth/classificação , Doença de Charcot-Marie-Tooth/epidemiologia , Criança , Análise Mutacional de DNA , Progressão da Doença , Feminino , Genes Dominantes , Ligação Genética , Humanos , Masculino , Condução Nervosa , Linhagem , Fenótipo , Polônia/epidemiologia , Tempo de ReaçãoRESUMO
Congenital hypomyelinating neuropathy (CHN; MIM# 605253) is a severe neuropathy with early infancy onset inherited as an autosomal dominant or recessive trait. Sural nerve biopsy shows a characteristic picture of nonmyelinated and poorly myelinated axons with basal lamina onion bulbs and lack of myelin breakdown products. Several mutations in the MTMR2, PMP22, EGR2, and MPZ genes have been found in patients with CHN. The authors describe the clinical and morphologic features of a patient with CHN and the identification of a novel Thr124Lys mutation in the MPZ gene.
Assuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Neuropatia Hereditária Motora e Sensorial/genética , Mutação de Sentido Incorreto , Proteína P0 da Mielina/genética , Mutação Puntual , Anormalidades Múltiplas/genética , Substituição de Aminoácidos , Criança , Doenças em Gêmeos , Éxons/genética , Genes Dominantes , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/congênito , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Neuropatia Hereditária Motora e Sensorial/patologia , Humanos , Masculino , Microscopia Eletrônica , Hipotonia Muscular/congênito , Hipotonia Muscular/genética , Proteína P0 da Mielina/química , Fibras Nervosas Mielinizadas/patologia , Polimorfismo Conformacional de Fita Simples , Reflexo Anormal , Escoliose/genética , Nervo Sural/fisiopatologia , Nervo Sural/ultraestruturaRESUMO
OBJECTIVE: The aim of these modeling studies on the generation of motor unit potentials (MUPs) was to establish the influence of MU parameters and recording conditions on the shape irregularity of MUPs. The focus was on the dependence of the irregularity of MUPs on fiber density, fiber diameters and the recording distance from the end-plate zone. METHODS: The study was performed using the 'EMG Simulator' software for modeling of MUP and our own software for calculations. RESULTS: The results indicate that the irregularity of a MUP increases with increased recording distance from the end-plate zone and decreases with increased fiber diameter and/or with increased fiber density. The quantitative relationship between these factors has been derived. CONCLUSIONS: The relationships determine the structural conditions in which irregular potential may be generated and therefore may be helpful in the interpretation of atypical MUPs.
Assuntos
Modelos Neurológicos , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Junção Neuromuscular/fisiologia , Potenciais de Ação , Simulação por Computador , Eletrodos , Eletromiografia/instrumentação , Humanos , Placa Motora/fisiologia , Fibras Musculares Esqueléticas/ultraestrutura , Músculo Esquelético/inervação , Músculo Esquelético/ultraestruturaRESUMO
Charcot-Marie-Tooth type 1B disease is a demyelinating neuropathy caused by mutations in the Myelin Protein Zero gene. It is inherited in an autosomal dominant fashion. So far only a few patients with a focally folded myelin phenotype on nerve biopsy have been shown to have mutations in the Myelin Protein Zero gene. In this report we describe a Polish patient with Charcot-Marie-Tooth type 1B disease. Sural nerve biopsy demonstrated focally folded myelin. Molecular genetic analysis of the coding region of the Myelin Protein Zero gene revealed a novel mutation, Thr65Ala, in exon 2 of the Myelin Protein Zero gene.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Mutação , Proteína P0 da Mielina/genética , Bainha de Mielina/patologia , Adulto , Alanina/genética , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/metabolismo , Doença de Charcot-Marie-Tooth/patologia , Análise Mutacional de DNA/métodos , Feminino , Deformidades da Mão/etiologia , Humanos , Microscopia Eletrônica/métodos , Atrofia Muscular/etiologia , Bainha de Mielina/genética , Bainha de Mielina/ultraestrutura , Dobramento de Proteína , Treonina/genéticaAssuntos
Doença de Charcot-Marie-Tooth/genética , Conexinas/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mosaicismo , Adolescente , Adulto , Idoso , Substituição de Aminoácidos , Sequência de Bases , Códon/genética , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Proteína beta-1 de Junções ComunicantesRESUMO
We reported three cases (two familial and one sporadic) of X-linked Emery-Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients demonstrated a typical inclusion body myositis (IBM)-like morphology. The third patient had only minor changes. Patients had elbow and ankle contractures, progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker implantation in all). There was a mutation within the Xq28 gene and complete absence of emerin in the nuclear membrane. Mononuclear cell infiltrations, rimmed vacuoles, amyloid deposits, as well as cytoplasmic and nuclear tubulofilamentous muscle inclusions were most unusual findings. Coexistence of IBM-like morphology and X-linked recessive EDMD might indicate that pathological features of IBM are nonspecific and may be present in other neuromuscular disorders.
Assuntos
Cromossomos Humanos X , Saúde da Família , Distrofia Muscular de Emery-Dreifuss/complicações , Miosite de Corpos de Inclusão/complicações , Adulto , Análise Mutacional de DNA , Ligação Genética , Humanos , Imuno-Histoquímica/métodos , Masculino , Proteínas de Membrana/metabolismo , Microscopia Eletrônica/métodos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/ultraestrutura , Distrofia Muscular de Emery-Dreifuss/genética , Distrofia Muscular de Emery-Dreifuss/patologia , Mutação , Miosite de Corpos de Inclusão/genética , Miosite de Corpos de Inclusão/patologia , Proteínas Nucleares , Timopoietinas/metabolismoRESUMO
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.