Abstract
Infantile-onset ascending spastic paralysis (OMIM #607225) is a rare autosomal recessive early onset motor neuron disease caused by mutations in the gene ALS2. We report on a splice acceptor site mutation in intron 9 of ALS2 (IVS9-2A>T) in a German patient from nonconsanguineous parents. The mutation results in skipping of exon 10. This causes a frame-shift in exon 11 and a premature stop codon. Analysis of the parental ALS2 gene revealed heterozygosity for the mutation in the mother but not in the father. Therefore, we studied polymorphic markers scattered along chromosome 2 in both parents and the patient and found maternal uniparental disomy in the patient. While homozygosity was observed at several loci of chromosome 2 including ALS2, other loci were heterozygous, i.e., both maternal alleles were present. The findings can be explained by at least four recombination events during maternal meiosis followed by a meiosis I error and postzygotic trisomy rescue or gamete complementation.
Original language | English |
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Pages (from-to) | 59-64 |
Number of pages | 6 |
Journal | Neurogenetics |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - Feb 2009 |
Keywords
- ALS2
- IAHSP
- Infantile-onset ascending spastic paralysis
- Splice site mutation
- Uniparental disomy