title: Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene.
abstract: Patients with autosomal recessive spinal muscular atrophy (SMA) usually carry a homozygous deletion of exons 7 and 8 of the telomeric survival motor neuron (SMN(T)) gene, although an isolated deletion of SMN(T) exon 8 has never been found. We now report on 2 patients with the typical features of SMA types II and III, who carried a homozygous deletion of SMN(T) exon 8 but retained SMN(T) exon 7. Importantly, to exclude a sequence conversion event of telomeric exon 8, we amplified a fragment that spanned exons 7 and 8 of the SMN gene. The resulting 1,010-base pair (bp) fragments were subjected to nested polymerase chain reaction (PCR) of exon 7. The subsequent restriction analysis failed to show any products of telomeric exon 7, as the site for primer 541C1120 was lost in both alleles. These findings indicate a homozygous deletion of SMN(T) exon 8. Direct sequencing of the cloned 1,010-bp fragment further confirmed that these 2 SMA patients did not possess telomeric exon 8. The more severely affected child also showed a deletion of the neuronal apoptosis inhibitory protein (NAIP) gene. The present findings provide evidence that an isolated deletion of SMN(T) exon 8 is associated with the milder subtypes of SMA. Our data also demonstrate that the additional deletion of the NAIP gene exacerbates the severity of the disease.
authors.affiliation: Institute of Neurology, School of Medicine, Catanzaro, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gambardella
authors.forename: R
authors.initials: R
authors.lastname: Mazzei
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: G
authors.initials: G
authors.lastname: Annesi
authors.forename: A
authors.initials: A
authors.lastname: Pasqua
authors.forename: F
authors.initials: F
authors.lastname: Annesi
authors.forename: F
authors.initials: F
authors.lastname: Quattrone
authors.forename: R L
authors.initials: RL
authors.lastname: Oliveri
authors.forename: P
authors.initials: P
authors.lastname: Valentino
authors.forename: F
authors.initials: F
authors.lastname: Bono
authors.forename: U
authors.initials: U
authors.lastname: Aguglia
authors.forename: M
authors.initials: M
authors.lastname: Zappia
authors.forename: G
authors.initials: G
authors.lastname: Vita
authors.forename: A
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000328:Adult; D002648:Child; D017362:Cyclic AMP Response Element-Binding Protein; D004576:Electromyography; D005091:Exons; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017384:Sequence Deletion
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins