Abstract
Sixty-four unrelated patients with infantile Krabbe disease (globoid cell leukodystrophy, GLD) of Dutch (n=41) or other European origin (n=23) were screened for the presence of a large 30kb deletion starting in intron 10 (IVS 10del30kb), a base substitution 1538T(T513M) and a polymorphism, 502T. The deletion and the T513M mutation were present in 52% and 8.5%, respectively, of the 82 GALC alleles of the Dutch patients. The 502T polymorphism, which had an allele frequency of 5.3% in a Dutch control panel, occurred in 65% of the GLD alleles. Analysis of patients and both parents in 26 of the families showed that del30kb was invariably associated with 502T. However, 502T was also present on 40% of the GLD alleles with an as yet unidentified mutation, which is 7.5 times higher than its frequency in controls. This suggests that besides del30kb at least one other relatively frequent mutation has arisen on the 502T GALC allele. A relatively high incidence of del30kb was also found in 23 other European (non-Dutch) patients (allele frequency 35%), but T513M did not occur in this group. Practical examples described in this report illustrate the potential usefulness of mutation analysis in many families with Krabbe disease for heterozygote detection and prenatal diagnosis.
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Kleijer, W.J., Keulemans, J.L.M., van der Kraan, M. et al. Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and other European origin. J Inherit Metab Dis 20, 587–594 (1997). https://doi.org/10.1023/A:1005315311165
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DOI: https://doi.org/10.1023/A:1005315311165