MOLECULAR ANALYSIS OF SURVIVAL MOTOR-NEURON (SMN) AND NEURONAL APOPTOSIS INHIBITORY PROTEIN (NAIP) GENES OF SPINAL MUSCULAR-ATROPHY PATIENTS AND THEIR PARENTS

We have assayed deletions of two candidate genes for spinal muscular a trophy (SMA), the survival motor neuron (SMN) and neuronal apoptosis i nhibitory protein (NAIP) genes, in 101 patients from 86 Chinese SMA fa milies. Deletions of exons 7 and 8 of the telomeric SMN gene were dete cted in 100%, 78.6%, 96.6%, and 16.7%, in type I, II, III, and adult-o nset SMA patients, respectively. Deletion of exon 7 only was found in eight type II and one type III patient. One type II patient did not ha ve a deletion of either exon 7 or 8. The prevalence of deletions of ex ons 5 and 6 of the NAIP gene were 22.5% and 2.4% in type I and II SMA patients, respectively. We also examined four polymorphisms of SMN gen es and found that there were only two, SMN-2 and (C)BCD541-2, in Chine se subjects. In our study, analysis of the ratio of the telomeric to c entromeric portion (T/C ratio) of the SMN gene after enzyme digestion was performed to differentiate carriers, normals, and SMA patients. We found the T/C ratio of exon 7 of the SMN gene differed significantly among the three groups, and may be used for carrier analysis. An asymp tomatic individual with homozygous deletion of exons 7 and 8 of the SM N gene showed no difference in microsatellite markers in the SMA-relat ed 5q11.2-5q13.3. In conclusion, SMN deletion in clinically presumed c hild-onset SMA should be considered as confirmation of the diagnosis. However, adult-onset SMA, a heterogeneous disease with phenotypical si milarities to child-onset SMA, may be caused by SMN or other gene(s).