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Genetic Heterogeneity and Clinical Outcome in a Swedish Family with Retinal Degeneration Caused by Mutations in CRB1 and ABCA4 Genes

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Genetic mechanisms underlying severe retinal dystrophy in a large Swedish family presenting two distinct phenotypes, Leber congenital amaurosis and Stargardt disease were investigated. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was a compound heterozygous for c.5461-10T>C and a novel ABCA4 mutation c.4773+3 A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants.

Our results provide evidence of genetic complexity causative of different clinical features present in the same family, which is an obvious challenge for ophthalmologists, molecular geneticists and genetic counsellors.

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Abbreviations

ABCA4 :

ATP-binding cassette, sub-family A (ABC1), member 4

APEX:

Arrayed primer extension

CRB1 :

Crumbs homolog 1 (Drosophila)

ERG:

Electroretinography

LCA:

Leber congenital amaurosis

ROH:

Region of homozygosity

RP:

Retinitis pigmentosa

RPE:

Retinal pigment epithelium

STGD1:

Stargardt disease

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Acknowledgments

This study was supported by grants from Visare Norr, KMA and University Hospital of Umeå.

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Authors and Affiliations

  1. Department of Medical Biosciences/Medical and Clinical Genetics, University Hospital of Umeå, SE 901 85, Umeå, Sweden

    Frida Jonsson, Anna Norberg & Irina Golovleva

  2. Department of Clinical Sciences/Ophthalmology, University of Umeå, SE 901 85, Umeå, Sweden

    Marie S. Burstedt & Ola Sandgren

Authors
  1. Frida Jonsson
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  2. Marie S. Burstedt
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  3. Ola Sandgren
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  4. Anna Norberg
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  5. Irina Golovleva
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Corresponding author

Correspondence to Irina Golovleva .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Jonsson, F., Burstedt, M., Sandgren, O., Norberg, A., Golovleva, I. (2014). Genetic Heterogeneity and Clinical Outcome in a Swedish Family with Retinal Degeneration Caused by Mutations in CRB1 and ABCA4 Genes. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_23

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_23

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

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