| Abstrakt: |
SMA, spinal muscular atrophy, is one the most common autosomal recessive disorders with an incidence of approximately 1:10.000. The disease is divided into three groups, which is based on the severity of the disease: type I (Werdnig-Hoffman disease) is the most severe, type II (intermediate) and type III (Kugelberg-Welander) the mildest form. The majority of the patients, > 95%, have a homozygous deletion (gene conversion) of SMN1, the SMA- determining gene. It now generally accepted that SMN2, which almost identical to SMN1, can modify the severity of SMA and several reports support the hypothesis that the copy number of SMN2 is inversely related to the severity of the disease. We have used the method MLPA (multiplex ligation-dependent probe amplification) to determine the copy number of both SMN1 and SMN2. Using the SMN-kit from mrc. Holland we have determined the copy number of SMN2 in 82 patients already known to be homozygous deleted for SMN1. The method turned out to be highly reliable, and all our patients could be unambiguously placed into four groups with 1,2, 3 or 4 copies of SMN2, which correlated with the type of the disease. The copy number of both SMN1 and SMN2 (exon 7 and 8) is determined in a single analysis and is easier than previously reported methods, where SMN1 and SMN2 copy-numbers is analysed separately. [ABSTRACT FROM AUTHOR] |
