Maternal uniparental heterodisomy with partial isodisomy of a chromosome 2 carrying a splice acceptor site mutation (IVS9-2A>T) in ALS2 causes infantile-onset ascending spastic paralysis (IAHSP)

Thilo Herzfeld, Nicole Wolf, Pia Winter, Holger Hackstein, Daniel Vater, Ulrich Müller*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)59-64
Number of pages6
JournalNeurogenetics
Volume10
Issue number1
DOIs
Publication statusPublished - Feb 2009

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