molecular prenatal and postnatal diagnosis of dmd/bmd in iranian population

duchenne muscular dystrophy (dmd), one of the most common and most severe hereditary muscle diseases, is transmitted as an x-linked recessive trait and is usually fetal before the third decade of life. dmd usually presents between the ages of 2 and 5 with severe, progressive muscle weakness and delayed motor milestones. muscle enzymes in the serum including creatine kinase levels are extremely elevated. the children are wheelchair bound by about 12 years of age. the incidence is about one in 3,500 male new-borns. an estimated 1/3 of cases are sporadic (new mutations). the carrier females are usually normal. however, in about two-thirds of female carriers the kc level is higher than normal range. becker muscular dystrophy (bmd) follows a similar but less severe clinical course than dmd. patients are usually ambulatory through 16 years of age and life expectancy may be normal. the disease has an incidence rate of one in 30,000 males. dmd and bmd are allelic variants, i.e. diseases caused by mutations in the same gene. the dmd gene spans more than 2500 kb (2.5 mb) on the long arm of the x chromosome. the severe dmd form is caused by the absence of detectable dystrophin, which at the dna level is usually a result of mutations that alter the reading frame leading to the production of a truncated dystrophin molecule. the milder bmd usually results from mutations that do not disrupt the reading frame so that a partially functional protein is produced. the large size of the dystrophin gene increases the probability of mutations of the gene. in approximately 65% of the dmd/bmd patients, the genetic defect is a deletion into so-called hot spot regions of the gene (the 5 end of the gene and exons 44-53). our deletion test is based on the pcr amplification of selected exons in these hot spots. at the present study, we screened large number of dmd/bmd patients for dystrophin deletion and our data indicate that the most of the deletions located in exons 45 to 52 which are in agreement with those findings in european dmd/bmd patients so-called hot spot regions (exons 44-53). furthermore the frequent deletion was exon 50 in iranian dmd/bmd patients. for the 65% of patients who have detectable mutations, the dna analysis not only confirms the diagnosis but allows for prenatal diagnosis for at risk relatives. for carrier and prenatal diagnostics in families with undefined mutations (the remaining 35%) the indirect linkage approach may be used. in this regards, at the department of neurogenetics, iranian centre of neurological research, tehran university of medical sciences, we are running a project to identify the most informative linked str and rflp dna markers to dystrophin gene and evaluating its accuracy in 40 iranian families with at least one effected dmd or bmd patient. the results will be very useful for confirmation and prenatal diagnosis of dmd or bmd in iranian families with non deletional dmd or bmd.