Motor system abnormalities in heterozygous relatives of a D90A homozygous CuZn-SOD ALS patient of Finnish extraction.
1999 (English)In: Journal of Neurological Sciences, ISSN 1302-1664, Vol. 169, no 1-2, 49-55 p.Article in journal (Refereed) Published
Presently, 64 mutations in the gene encoding the enzyme CuZn-superoxide dismutase have been found in a small fraction of amyotrophic lateral sclerosis patients worldwide. All but one of these mutations show autosomal dominant inheritance. In Scandinavia, the D90A mutation is inherited as an autosomal recessive trait and patients have an easily recognizable characteristic phenotype with little variation among patients, even amongst different families. Importantly, all D90A heterozygous relatives of Scandinavian D90A homozygous patients have been reported as clinically unaffected. We have investigated a Canadian family of Finnish extraction in which the D90A homozygous proband developed ALS with the characteristic phenotype. Remarkably, two D90A heterozygous relatives show slight symptoms and signs of motor system involvement, suggesting that the final phenotype of an individual with a CuZn-superoxide dismutase mutation is shaped by the combination of the particular CuZn-SOD mutation, other polymorphic modifying genes elsewhere in the genome, stochastics and possible environmental factors.
Place, publisher, year, edition, pages
1999. Vol. 169, no 1-2, 49-55 p.
IdentifiersURN: urn:nbn:se:umu:diva-4836DOI: 10.1016/S0022-510X(99)00215-4PubMedID: 10540007OAI: oai:DiVA.org:umu-4836DiVA: diva2:144087