Molecular Analysis of the Neuronal Apoptosis Inhibitory Protein Gene in Families with Spinal Muscular Atrophy

Background: Spinal muscular atrophy is an autosomal recessive disorder characterized by degeneration of anterior horn cells in the spinal cord leading to progressive muscular weakness and atrophy. The spinal muscular atrophy candidate interval genes including survival motor neuron, the responsible gene in spinal muscular atrophy phenotype expression, neuronal apoptosis inhibitory protein, and P44, potential modifying genes, are located on chromosome 5q13 in two highly homologous copies (telomeric and centromeric) within the spinal muscular atrophy region. Methods: In this study, the neuronal apoptosis inhibitory protein gene deletion was analyzed in 34 spinal muscular atrophy families, with the consanguinity rate of 65% (22/34), in whom exon 7 of the survival motor neuron-1 gene was already confirmed and was deleted in 79% of the affected individuals. Deletion analysis of exons 5, 6, and 13 of the neuronal apoptosis inhibitory protein-t gene was carried out in our samples. Results: We found 80% neuronal apoptosis inhibitory protein gene deletion in 5q-spinal muscular atrophy patients (91% spinal muscular atrophy-I, 50% spinal muscular atrophy-II and -III), and in 5% (two of fourty) of spinal muscular atrophy parents. All the neuronal apoptosis inhibitory protein-deleted samples also lacked the survival motor neuron-1 gene. Conclusion: The neuronal apoptosis inhibitory protein gene deletion in spinal muscular atrophy-I was higher than the other spinal muscular atrophy types. The high frequency of neuronal apoptosis inhibitory protein deletion most likely reflects a higher frequency of survival motor neuron-1 deletions compared with survival motor neuron-1 to survival motor neuron-2 gene conversion in this population.