RESUMO
OBJECTIVE: Description of 8 new ANO5 mutations and significant expansion of the clinical phenotype spectrum associated with previously known and unknown mutations to improve diagnostic accuracy. METHODS: DNA samples of 101 patients in 95 kindreds at our quaternary referral center in Finland, who had undetermined limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic evaluation, and the clinical findings of patients with mutations were retrospectively analyzed. RESULTS: A total of 25 patients with muscular dystrophy caused by 11 different recessive mutations in the ANO5 gene were identified. The vast majority of mutations, 8 of 11, proved to be previously unknown new mutations. The most frequent mutation, c.2272C>T (p.R758C), was present in 20 patients. The phenotypes associated with this and the common European mutation, c.191dupA, varied from nearly asymptomatic high hyperCKemia to severe LGMD with consistently milder phenotypes in female patients. CONCLUSIONS: Mutations in ANO5 are a frequent cause of undetermined muscular dystrophy, with both distal and proximal presentation. Other types include high hyperCKemia, myalgia, or calf hypertrophy over decades without significant weakness, especially in female patients. Mutations are distributed all over the gene, indicating that muscular dystrophy caused by ANO5 can be expected to occur in all populations.
Assuntos
Canais de Cloreto/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Mutação/fisiologia , Adulto , Idade de Início , Idoso , Anoctaminas , Western Blotting , Estudos de Coortes , Creatina Quinase/sangue , DNA/genética , Feminino , Finlândia , Genes Recessivos , Testes Genéticos , Variação Genética , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Fenótipo , Reprodutibilidade dos TestesRESUMO
Hyperostosis is a volume-unit osseous increase of very diverse etiology. We present the case of a 68-year woman with a cranial hyperostosis debuting with frontal protrusion, headache and neurologic symptoms. Image proves demonstrated a hyperostosis in the calotte and meningeal enhancement, without intracerebral lesions nor malignant cells in the cerebrospinal fluid. Analytic data were unspecific. Cranial biopsy showed huge neoplastic infiltration in bone and meninges. Primary site remained unknown after a CAT and a mammography.
Assuntos
Adenocarcinoma/secundário , Hiperostose Frontal Interna/diagnóstico , Neoplasias Meníngeas/secundário , Neoplasias Primárias Desconhecidas , Neoplasias Cranianas/secundário , Adenocarcinoma/complicações , Idoso , Feminino , Humanos , Hiperostose Frontal Interna/etiologia , Neoplasias Meníngeas/complicações , Neoplasias Cranianas/complicaçõesRESUMO
La hiperostosis es un aumento de masa ósea por unidad de volumen de etiología muy diversa. Presentamos el caso de una mujer de 68 años con hiperostosis craneal que debutó con clínica de protusión frontal derecha, cefalea y sintomatología neurológica. Las pruebas de imagen demostraron la existencia de hiperostosis de calota con afectación meníngea, sin lesiones cerebrales ni células malignas en líquido cefalorraquídeo. Los datos analíticos eran inespecíficos. La biopsia craneal mostró amplia infiltración neoplásica por adenocarcinoma metastásico tanto en hueso como en meninges. No se localizó el tumor primario tras realizarse TAC y mamografía (AU)