Patients with autosomal recessive spinal muscular atrophy (SMA) usually carry a homozygous deletion of exons 7 and 8 of the telomeric survival motor neuron (SMNT) gene, although an isolated deletion of SMNT 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 SMNT exon 8 but retained SMNT 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 SMNT 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 SMNT 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

Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene

ZAPPIA, MARIO;
1998-01-01

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 (SMNT) gene, although an isolated deletion of SMNT 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 SMNT exon 8 but retained SMNT 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 SMNT 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 SMNT 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
File in questo prodotto:
File Dimensione Formato  
Spinal muscular atrophy due.pdf

solo gestori archivio

Tipologia: Versione Editoriale (PDF)
Dimensione 613.75 kB
Formato Adobe PDF
613.75 kB Adobe PDF   Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/60974
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 36
  • ???jsp.display-item.citation.isi??? 31
social impact