Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14

doi:10.1016/0140-6736(90)91803-I

The Lancet

Volume 336, Issue 8710, 4 August 1990, Pages 271-273

https://doi.org/10.1016/0140-6736(90)91803-I Get rights and content

Abstract

Linkage analysis in twenty-five families with acute (type I) spinal muscular atrophy (SMA) showed that the mutant gene responsible for the disorder is tightly linked to the D5S39 locus. The mutation(s) causing the intermediate (type II) and juvenile chronic (type III) forms of SMA were also mapped to DNA marker D5S39 on chromosome 5 (5q12-q14). Thus, the three forms, which have been differentiated clinically on the basis of age of onset and clinical course, are most probably due to different mutations at a single locus on chromosome 5. Prenatal diagnosis of SMA type I will now be possible.

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Citation Excerpt :
The gene for spinal muscular atrophy was initially located on Chromosome 5q by Gilliam et al and Brzustowicz et al in 1990 [5,6] in a cohort of intermediate severity cases from an inbred Amish community and confirmation in the severe form followed soon after. Because of the complexity of their duplicated region of chromosome 5 it took several years for Melki's group [7–10] to identify the gene. They named it survival motor neurone gene (SMN).
Findings from mice that had their Smn gene deleted and some copies of the human SMN2 gene introduced to produce SMN protein are summarized. Symptoms due to this manipulation can be corrected only by restoring the SMN protein expression in neurones and not in muscle. The changes in muscle and neuromuscular junction (NMJ) in these mutant mice are probably due to the malfunction of the neuronal component of the NMJ i.e. the nerve terminal. The reduction of transmitter release by nerve terminals in animals with reduced SMN protein supports this notion. There is a critical period during which the presence of the SMN protein is mandatory for the survival of the motor unit and the individual. This period coincides with the most important events involved in the development of the motor unit. Results from normal genetically unaffected rats and mice show that during a critical period of development the function of the nerve terminal and the release of transmitter play a crucial role in the development of the motor neurone and muscle. The possibility that targeting the function of the nerve terminal to overcome its inability to release transmitter could benefit patients with the deletion of the SMN gene.

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Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14

Abstract

Lancet

J Neurol Sci

J Mol Biol

Cell

Genomics

Lancet

Selective and non-selective susceptibility of muscle fibre types

Arch Neurol

Motor nerve conduction velocity in spinal muscular atrophy of childhood

Arch Dis Child

Infantile muscular atrophy. A progressive study with particular reference to a slowly progressive variety.

Brain