Assuntos
Doença da Arranhadura de Gato/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Animais , Axônios/patologia , Biópsia , Doença da Arranhadura de Gato/patologia , Gatos , Pré-Escolar , Humanos , Masculino , Fibras Nervosas Mielinizadas/patologia , Exame Neurológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Nervo Sural/patologiaRESUMO
We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteínas da Mielina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Doença de Charcot-Marie-Tooth/classificação , DNA/genética , Modelos Animais de Doenças , Expressão Gênica , Humanos , Camundongos , Camundongos Mutantes Neurológicos , Dados de Sequência Molecular , Família Multigênica , Mutação PuntualRESUMO
The patient described is a 14-year-old girl who suffered from an oculocutaneous albinism. The developmental milestones were reached with some delay. Gradually she experienced fatiques, and wasting of the pelvic girdle muscles and weakness appeared. In suralis nerve biopsy sections no abnormalities were found. In muscle biopsy sections the characteristic findings of a primary central neuronal muscular atrophy were seen. Based on clinical and histopathological findings it may be stated that the patient is suffering from a motor neuron disease. The chance of the combined occurrence of oculocutaneous albinism and motor neuron disease can be estimated to be one out of 750 X 10(6), unless an incestuous relation is supposed.
