N. Roy et al., THE GENE FOR NEURONAL APOPTOSIS INHIBITORY PROTEIN IS PARTIALLY DELETED IN INDIVIDUALS WITH SPINAL MUSCULAR-ATROPHY, Cell, 80(1), 1995, pp. 167-178
The spinal muscular atrophies (SMAs), characterized by spinal cord mot
or neuron depletion, are among the most common autosomal recessive dis
orders. One model of SMA pathogenesis invokes an inappropriate persist
ence of normally occurring motor neuron apop tosis. Consistent with th
is hypothesis, the novel gene for neuronal apoptosis inhibitory protei
n (NAIP) has been mapped to the SMA region of chromosome 5q13.1 and is
homologous with baculoviral apoptosis inhibitor proteins. The two fir
st coding exons of this gene are deleted in approximately 67% of type
I SMA chromosomes compared with 2% of non-SMA chromosomes. Furthermore
, RT-PCR analysis reveals internally deleted and mutated forms of the
NAIP transcript in type I SMA individuals and not in unaffected indivi
duals. These findings suggest that mutations in the NAIP locus may lea
d to a failure of a normally occurring inhibition of motor neuron apop
tosis resulting in or contributing to the SMA phenotype.