title: Clinical application of the molecular diagnosis of spinal muscular atrophy: deletions of neuronal apoptosis inhibitor protein and survival motor neuron genes.
abstract: The molecular genetic diagnosis of spinal muscular atrophy (SMA) has recently been complicated by the identification of two candidate genes, which are often deleted in affected individuals but are also occasionally deleted in apparently unaffected carriers. We present a compilation of genotypes, from our laboratory and recent reports, for the survival motor neuron (SMN) and neuronal apoptosis inhibitor protein (NAIP) genes. Bayesian analyses were used to generate probabilities for SMA when deletions are present or absent in SMN. We found that when the SMN(T) exon 7 is deleted, the probability of SMA can reach greater than 98% in some populations, and when SMN(T) is present, the probability of SMA is approximately 17 times less than the prior population risk. Deletion of NAIP exon 5, as well as SMN(T) exon 7, is associated with a 5-fold increased risk of type I SMA. Case studies are used to illustrate differing disease risks for pre- and postnatal testing, depending on the presence of information about clinical status or molecular results. These analyses demonstrate that deletion screening of candidate genes can be a powerful tool in the diagnosis of SMA.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Somerville
authors.forename: A G
authors.initials: AG
authors.lastname: Hunter
authors.forename: H L
authors.initials: HL
authors.lastname: Aubry
authors.forename: R G
authors.initials: RG
authors.lastname: Korneluk
authors.forename: A E
authors.initials: AE
authors.lastname: MacKenzie
authors.forename: L C
authors.initials: LC
authors.lastname: Surh
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein; D010375:Pedigree; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C496800:NAIP protein, human; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins