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

Abstract

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