Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) (original) (raw)

Abstract

We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis, intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

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Acknowledgments

This study has been supported by a grant of the Deutsche Forschungsgemeinschaft (SCHO 754/5-1) and funding from the e-rare program to EUROSPA (01GM0807) and an EC grant (TECHGENE; FP7-Health 2007-B223143).

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Authors and Affiliations

  1. Department of Medical Genetics, University of Tübingen, Tübingen, Germany
    Peter Bauer, Nina Schlipf, Christopher Schröder & Olaf Riess
  2. Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel
    Esther Leshinsky-Silver, Lubov Blumkin & Tally Lerman-Sagie
  3. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    Esther Leshinsky-Silver, Lubov Blumkin & Tally Lerman-Sagie
  4. Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    Esther Leshinsky-Silver & Dorit Lev
  5. Pediatric Neurology Unit, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    Lubov Blumkin & Tally Lerman-Sagie
  6. Department of Neurology, Hertie-Institute of Clinical Brain Research and German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany
    Julia Schicks & Ludger Schöls
  7. Institute of Medical Genetics, Wolfson Medical Center, Holon, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
    Dorit Lev

Authors

  1. Peter Bauer
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  2. Esther Leshinsky-Silver
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  3. Lubov Blumkin
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  4. Nina Schlipf
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  5. Christopher Schröder
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  6. Julia Schicks
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  7. Dorit Lev
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  8. Olaf Riess
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  9. Tally Lerman-Sagie
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  10. Ludger Schöls
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Corresponding author

Correspondence toEsther Leshinsky-Silver.

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Peter Bauer, Esther Leshinsky-Silver, and Lubov Blumkin contributed equally to this work.

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Bauer, P., Leshinsky-Silver, E., Blumkin, L. et al. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47).Neurogenetics 13, 73–76 (2012). https://doi.org/10.1007/s10048-012-0314-0

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