MOLECULAR DIAGNOSIS IN IRANIAN PATIENTS WITH SPINAL MUSCULAR ATROPHY

BACKGROUND—Spinal muscular atrophies (SMA) are a group of heterogeneous disorders characterized by the degeneration of the lower motor neurons of the ventral horns of the spinal cord. They are inherited by an autosomal recessive pattern, and because of the high rate of consanguinity in the Iranian population the incidence of these diseases is very high in this region. The precise frequency has not been determined. We set up molecular tests for the diagnosis of affected patients, carrier detection, and prenatal diagnosis for high risk pregnancies. MATERIALS AND METHODS—We investigated the presence or absence of the survival motor neuron (SMN) gene in 47 Iranian families, including 60 patients by polymerase chain reaction 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. RESULTS—Mutation detection in the 22 live patients showed that in the 21 cases, both alleles were deleted. In 1 case only one of the mutations was detected, therefore the other must have been a point mutation. In 34 families, both of the parents were carriers, that is, they carried only one copy of the normal SMN gene. In 9 of the couples only one mutation was detected, therefore in the other one, it should have been a point mutation that was not diagnosed. Molecular testing of 15 fetuses by prenatal diagnostic procedures showed that 4 of the fetuses were normal, 3 fetuses were affected and carried both of the mutations, five fetuses were carriers (they carried one of the mutations), and the other 2 were carriers or healthy, but only one case might have been carrier or affected. CONCLUSION—SMA is a very common disease in the Iranian population, due to the high frequency of consanguineous marriages. Preventive measures by genetic counseling, carrier detection, and prenatal diagnosis are helpful in the prevention of recurrences in the future pregnancies.