Journal Article

Detection of the Survival Motor Neuron (SMN) Genes by FISH: Further Evidence for a Role for <i>SMN2</i> in the Modulation of Disease Severity in SMA Patients

Tiziana Vitali, Vittorio Sossi, Francesco Tiziano, Stefania Zappata, Anna Giuli, Maria Paravatou-Petsotas, Giovanni Neri and Christina Brahe

in Human Molecular Genetics

Volume 8, issue 13, pages 2525-2532
Published in print December 1999 | ISSN: 0964-6906
Published online December 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.13.2525
Detection of the Survival Motor Neuron (SMN) Genes by FISH: Further Evidence for a Role for SMN2 in the Modulation of Disease Severity in SMA Patients

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Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder which presents with various clinical phenotypes ranging from severe to very mild. All forms are caused by the homozygous absence of the survival motor neuron (SMN1) gene. SMN1 and a nearly identical copy (SMN2) are located in a duplicated region at 5q13 and encode identical proteins. The genetic basis for the clinical variability of SMA remains unclear, but it has been suggested that the copy number of SMN2 could influence the disease severity. We have assessed the number of SMN2 genes in patients with different clinical phenotypes by fluorescence in situ hybridization (FISH) using as SMN probe a mixture of small specific DNA fragments. Gene copy number was established by FISH on interphase nuclei, but the presence of two SMN2 genes on the same chromosome could also be revealed by FISH on metaphase spreads. All patients had at least two SMN2 genes. We found two or three copies of SMN2 in severely affected type I patients, three copies in intermediately affected type II patients, generally four copies in mildly affected type III patients and four or eight copies in patients with very mild adult-onset SMA. No alterations of the genes were detected by Southern blot and sequence analysis, suggesting that all gene copies of SMN2 were intact. These data provide additional evidence that the SMN2 genes modulate the disease severity and suggest that knowledge of the gene copy number could be of some prognostic value.

Journal Article.  4814 words.  Illustrated.

Subjects: Genetics and Genomics

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