Identification of point mutations in Turkish DMD/BMD families using multiplex-single stranded conformation analysis (SSCA)

Small mutations are the cause of the disease in one third of cases of Duche nne and Becker muscular dystrophy (DMD/BMD), The identification of point mu tations in the dystrophin gene is considered to be very important, because it may provide new insights into the function of dystrophin and direct info rmation for genetic counselling, In this study, we have screened 18 deletio n-prone exons (25.5% of the coding region) of the dystrophin gene by using a modified non-isotopic multiplex single-stranded conformation analysis (SS CA). Mutations responsible for the disease phenotype could be identified in five out of 56 unrelated DMD/BMD patients without detectable deletions, Tw o of these mutations, 980-981delCC and 719G > C, are novel mutations which have not been described previously. Four of the five mutations, including 9 80-981delCC detected in this study are found to be nonsense or frameshift m utations leading to the synthesis of a truncated dystrophin protein. The mi ssense mutation, 719G > C, causing the substitution of highly conserved ala nine residue at 171 with proline in the actin binding domain of the dystrop hin, is associated with a BMD phenotype. This study also revealed the prese nce of six polymorphisms in Turkish DMD/BMD patients.