Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy.

DNA studies in 103 spinal muscular atrophy (SMA) patients from The Netherlands revealed homozygosity for a survival motor neuron (SMN) deletion in 96 (93%) of 103. Neuronal apoptosis inhibitory protein deletions were found in 38 (37%) of 103 and occurred most frequently in SMA type I. SMN deletions have not yet been described to occur in healthy subjects. In this study, however, four unaffected sibs from two SMA families showed homozygosity for SMN deletions. Homozygosity for an SMN deletion in unaffected persons seems to be very rare. Therefore, demonstration of a homozygous SMN deletion in a clinically presumed SMA patient should be considered as a confirmation of the diagnosis, whether or not SMN is in fact the causal gene for SMA.

[1]  K. Davies,et al.  Deletions in the survival motor neuron gene on 5q13 in autosomal recessive spinal muscular atrophy. , 1995, Human molecular genetics.

[2]  J. Weissenbach,et al.  Identification and characterization of a spinal muscular atrophy-determining gene , 1995, Cell.

[3]  T. Crawford,et al.  The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy , 1995, Cell.

[4]  Benjamin Lewin,et al.  Genes for SMA: Multum in parvo , 1995, Cell.

[5]  D. Le Paslier,et al.  De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. , 1994, Science.

[6]  B. Wirth,et al.  Autosomal recessive proximal spinal muscular atrophy in 101 sibs out of 48 families: clinical picture, influence of gender, and genetic implications. , 1994, American journal of medical genetics.

[7]  H. Scheffer,et al.  Apparent SMA I unlinked to 5q. , 1994, Journal of medical genetics.

[8]  G. V. Ommen,et al.  Linkage and apparent heterogeneity in proximal spinal muscular atrophies , 1993, Neuromuscular Disorders.

[9]  M. Lathrop,et al.  Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14 , 1990, The Lancet.

[10]  T. Lehner,et al.  Genetic homogeneity between acute and chronic forms of spinal muscular atrophy , 1990, Nature.

[11]  M. Lathrop,et al.  Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q , 1990, Nature.

[12]  M. Leppert,et al.  Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q1 1.2–13.3 , 1990, Nature.

[13]  V. Dubowitz.  Muscle disorders in childhood. , 1977, Israel journal of medical sciences.

[14]  J. Pearn.  The Gene Frequency of Acute Werdnig-Hoffmann Disease (SMA Type 1). A Total Population Survey in North-East England , 1973, Journal of medical genetics.

[15]  A. Emery.  The nosology of the spinal muscular atrophies. , 1971, Journal of medical genetics.