title: The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.
abstract: The spinal muscular atrophies (SMAs), characterized by spinal cord motor neuron depletion, are among the most common autosomal recessive disorders. One model of SMA pathogenesis invokes an inappropriate persistence of normally occurring motor neuron apoptosis. Consistent with this hypothesis, the novel gene for neuronal apoptosis inhibitory protein (NAIP) has been mapped to the SMA region of chromosome 5q13.1 and is homologous with baculoviral apoptosis inhibitor proteins. The two first 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 individuals. These findings suggest that mutations in the NAIP locus may lead to a failure of a normally occurring inhibition of motor neuron apoptosis resulting in or contributing to the SMA phenotype.
authors: Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors: N
authors: N
authors: Roy
authors: M S
authors: MS
authors: Mahadevan
authors: M
authors: M
authors: McLean
authors: G
authors: G
authors: Shutler
authors: Z
authors: Z
authors: Yaraghi
authors: R
authors: R
authors: Farahani
authors: S
authors: S
authors: Baird
authors: A
authors: A
authors: Besner-Johnston
authors: C
authors: C
authors: Lefebvre
authors: X
authors: X
authors: Kang
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*
chemical_list: C496800:NAIP protein, human; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein