molecular analysis and pr enatal diagnosis of spinal muscular atrophy in iranian population: association of neural apoptosis inhibitory protein (naip) deletions with severity of the disease

defects in genes for survival motor neuron (smn) and neural apoptosis inhibitory proteins (naip) have been reported associated with spinal muscular atrophy (sma). among the genetic defects, deletions in exons 7 and 8 of smn and exons 4 and 5 of naip were found to be most significant. in the current study, 35 unrelated sma patients including 9 patients with type i, 6 with type ii, 20 with type iii/iv, as well as 34 cvs samples from carrier couples with at least one affected child were studied for deletions in smn and naip genes. deletions were investigated using pcr followed by restriction fragment length polymorphism (pcr/rflp) and gel electrophoresis. deletion frequency in smn (e7 and/or e8) and naip (e4 and/or e5) in patients with sma type i was 77.7%/ 77% in type ii 66%/ 100%, and in type iii/iv 45%/ 0.5%. the frequency of deletions in cvs samples was 90%/ 70% for smn and niap, respectively. moreover, homozygous deletion in e7 and/or e8 of the smn gene was found with high frequency in both type i (77%) and type ii (66%), and with a less frequency (45%) in type iii/iv. similarly, homozygous deletions of e4 and/or e5 of naip gene was highest in type i (77%) and type ii (100%) compare to type iii/iv (0.5%). these data suggested a strong association of deletions in e4 and e5 of naip gene together with deletions in smn gene (e7 and 8) with more severe form of sma type i and type ii in iranian population.