A NOVEL SPLICE-SITE MUTATION IN A BECKER MUSCULAR-DYSTROPHY PATIENT

A Becker muscular dystrophy patient was found to have a single base su bstitution at the 5' end of intron 54. This single base substitution d isrupts the invariant GT dinucleotide within the 5' donor splice site and was shown to cause an out of frame deletion of exon 54 during mRNA processing. This is predicted to produce a truncated dystrophin prote in which is more consistent with a DMD phenotype. However, small quant ities of normal mRNA are also transcribed and these are sufficient to produce a reduced amount of normal molecular weight dystrophin and giv e rise to a milder BMD phenotype. This indicates that a single base su bstitution at an invariant dinucleotide of the splice site consensus s equence may still allow read through of the message and allow the prod uction of some normal protein. This shows that there are a greater num ber of possible intronic mutations that can lead to a mild phenotype a nd it also underlines the importance of performing cDNA analysis when screening for small gene alterations in the BMD patient population.