Report of molecular diagnosis in iranian families with spinal muscular atrophy

ABSTRACT

Spinal muscular atrophies [SMA] are a group of heterogeneous disorders characterized by the degeneration of the lower motor neurons. The inheritance is by autosomal recessive pattern, and because of the high rate of consanguinity in the Iranian population the incidence of these diseases is common in this region, but the precise frequency has not been determined. To establish a clinical and molecular diagnosis for SMA in Iran, we have set up molecular tests for the diagnosis of affected patients, carrier detection, and prenatal diagnosis for high risk pregnancies. We investigated the presence or absence of the [SMN] gene in 47 Iranian families, including 60 patients by PCR amplification of exons 7 and 8 in affected individuals and parents of patients for carrier detection. In addition, prenatal testing was performed on 15 pregnant mothers. Mutation detection in the 22 live patients showed that in 21 cases, both alleles were deleted. In 1 case only one deletion was detected suggesting that the other allele must have a point mutation. In 34 families both of the parents were carriers, and carried only one copy of the normal SMN gene. In 9 couples a mutation was detected in one partner, suggesting that the other one had a point mutation that is not detected by this techniqe. Molecular testing of 15 fetuses showed that 4 of the fetuses were normal, 3 fetuses were affected carrying both mutations, five fetuses were carrier carrying one of the mutations, and of the remaining two were either carrier or healthy and only one was carrier or affected. Due to the high rate of consanguineous marriage, our study showed that this disorder is relating common, in the Iranian population. Preventive measures by genetic counseling, carrier detection, and prenatal diagnosis are now available and very helpful in the prevention of recurrence and in disease control