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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)

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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.

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Acknowledgment

We thank Dr. Dagmar Nolte for discussions.

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Authors and Affiliations

  1. Institut für Humangenetik, Justus-Liebig-Universität, Schlangenzahl 14, 35392, Giessen, Germany

    Thilo Herzfeld, Pia Winter & Ulrich Müller

  2. Klinik für Kinderneurologie, Universitätsklinikum, Im Neuenheimer Feld 150, 69120, Heidelberg, Germany

    Nicole Wolf & Daniel Vater

  3. Institut für Klinische Immunologie und Transfusionsmedizin, Justus-Liebig-Universität, Langhansstraße 7, 35392, Giessen, Germany

    Holger Hackstein

Authors
  1. Thilo Herzfeld
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  2. Nicole Wolf
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  3. Pia Winter
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  4. Holger Hackstein
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  5. Daniel Vater
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  6. Ulrich Müller
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Correspondence to Ulrich Müller.

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Thilo Herzfeld and Nicole Wolf contributed equally to this paper.

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Herzfeld, T., Wolf, N., Winter, P. et al. 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). Neurogenetics 10, 59–64 (2009). https://doi.org/10.1007/s10048-008-0148-y

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  • DOI: https://doi.org/10.1007/s10048-008-0148-y

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