A mutation in myotilin causes spheroid body myopathy.
Neurology
; 65(12): 1936-40, 2005 Dec 27.
Article
en En
| MEDLINE
| ID: mdl-16380616
ABSTRACT
BACKGROUND:
Spheroid body myopathy (SBM) is a rare, autosomal dominant, neuromuscular disorder, which has only been previously reported in a single large kindred. Identification of the mutated gene in this disorder may provide insight regarding abnormal neuromuscular function.METHODS:
The authors completed a detailed clinical evaluation on an extensive kindred diagnosed with SBM. Genome-wide linkage analysis was performed to localize the disease gene to a specific chromosomal region. Further marker genotyping and screening of a positional, functional candidate gene were completed to detect the disease-causing mutation. Pathologic analysis of muscle biopsy was performed on three individuals. Biochemical studies were performed on one muscle biopsy specimen from an affected individual.RESULTS:
Linkage to chromosome 5q23-5q31 was detected with a lod score of 2.9. Genotyping of additional markers in a larger sample of family members produced a maximum lod score of 6.1 and narrowed the critical interval to 12.2 cM. Screening of the candidate gene titin immunoglobulin domain protein (TTID, also known as MYOT) detected a cytosine-to-thymine mutation in exon 2 of all clinically affected family members. Similar pathologic changes were present in all muscle biopsy specimens. Immunohistologic and biochemical analysis revealed that the TTID protein, also known as myotilin, is a component of the insoluble protein aggregate.CONCLUSIONS:
A novel mutation in the TTID gene results in the clinical and pathologic phenotype termed "spheroid body myopathy." Mutations in this gene also cause limb-girdle muscular dystrophy 1A and are associated with myofibrillar myopathy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cuerpos de Inclusión
/
Músculo Esquelético
/
Predisposición Genética a la Enfermedad
/
Proteínas del Citoesqueleto
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Proteínas Musculares
/
Enfermedades Musculares
/
Mutación
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Neurology
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos