Molecular diagnosis of Duchenne muscular dystrophy

• Autor(a) principal: Sarlo, Laís Gomes
• Data de Publicação: 2009
• Outros Autores: da Silva, Antonio Francisco Alves, Medina-Acosta, Enrique
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Revista Científica da Faculdade de Medicina de Campos
• Texto Completo: https://www.fmc.br/ojs/index.php/RCFMC/article/view/130
• topic: análise de ligação; diagnóstico molecular indireto;; distrofia muscular Duchenne; microssatélites; marcadores polimórficos; sequenciamento; Duchenne muscular dystrophy; indirect molecular diagnosis;; linkage analysis; microsatellites; polymorphic markers; sequencing

Duchenne muscular dystrophy is the most frequent recessive X-linked genetic disease in humans, affecting 1 in 3500 born males. It is caused by mutations in the DMD gene, localized in the Xp21.2- Xp21.1 chromosomal region, which codes for dystrophin, a cytoskeleton protein found in the inner surface of muscle fibers. Pathogenic mutations are heterogeneous in nature and a considerably large number has been described. Approximately 2/3 of index cases are hereditary and the remaining 1/3 is due to de novo mutations. Direct molecular diagnosis of the etiology of the disease involves sequencing of the 79 exons for determination of mutations in affected males. This method is laborious and expensive, imiting its broad application, particularly in tracking mutation in women carriers. The identification of mutation carriers can be done indirectly by linkage analysis of microsatellites. Currently only dinucleotide microsatellites are known in 29 introns; 15o of which are used and they exhibit heterozigosity rates varying from 40 to 84% in various populations. The main drawback of genotyping dinucleotide microsatellites is the occurrence of stutter products, which differ in size by multiples of the repeat unit from the true allele. There is a need to invest in development of tetranucleotide and pentanucleotide microsatellites that result in significant reduction of stutter products and that enables accurate allele designation, diminishing the possibilities of error of diagnosis.