Human Molecular Genetics, Vol 5, 1971-1976, Copyright © 1996 by Oxford University Press
C Brahe, O Clermont, S Zappata, F Tiziano, J Melki and G Neri
Recently, a spinal muscular atrophy (SMA) determining gene, termed survival
motor neuron (SMN) gene, has been isolated from the 5q13 region and found
deleted in most patients. A highly homologous copy of this gene has also
been isolated and located in a centromeric position. We have analyzed 158
patients (SMA types I-IV) and found deletions of SMN exon 7 in 96.8%.
Mutations other than gross deletions seem to be extremely rare. In one of
the undeleted SMA type I patients, a newborn who survived for only 42 days,
we detected a maternally inherited 5 bp microdeletion in exon 3, resulting
in a premature stop codon. By RT-PCR and long range PCR amplification we
were able to show that the deletion belongs to the SMN gene, rather than to
the centromeric copy, and that the proposita had no paternal SMN gene.
Analysis of the neuronal apoptosis inhibitor protein (NAIP) gene, which
maps close to SMN and has been proposed as a SMA modifying gene, suggests
the presence of at least one full-length copy. Haplotype analysis of
closely linked polymorphic markers suggests that the proposita also lacks
the maternally derived copy of the centromeric homologue of SMN supporting
the hypothesis that the severity of the phenotype might depend on the
reduced number of centromeric genes in addition to the frameshift mutation.
ARTICLES
Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I
Istituto di Genetica Medica, Universita Cattolica del Sacro Cuore, Facolta di Medicina e Chirurgia A. Gemelli, Rome, Italy.
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