Identification of a novel deletion in the OA1 gene: report of the first Spanish family with X-linked ocular albinism

Authors

  • Monica Martinez-Garcia PhD,

    1. Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid,
    2. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
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    • These two authors contributed equally to this work.

  • Rosa Riveiro-Alvarez PhD,

    Corresponding author
    1. Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid,
    2. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
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    • These two authors contributed equally to this work.

  • Cristina Villaverde-Montero,

    1. Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid,
    2. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
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  • Diego Cantalapiedra PhD,

    1. Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid,
    2. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
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  • Blanca Garcia-Sandoval MD PhD,

    1. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
    2. Ophthalmology Department, Fundacion Jimenez Diaz, Madrid, Spain
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  • Carmen Ayuso MD PhD,

    1. Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid,
    2. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
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  • Maria Jose Trujillo-Tiebas PhD

    1. Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid,
    2. Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, and
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Dr Rosa Riveiro-Alvarez, Genetics and Genomics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz, Avd. Reyes Catolicos 2, 28040 Madrid, Spain. Email: rriveiro@fjd.es

Abstract

Background:  This study was undertaken to analyse the OA1 gene (GPR143) and its involvement in a Spanish family presenting with nystagmus, a common symptom of X-linked ocular albinism (XLOA).

Methods:  DNA samples from the index case and eight relatives were analysed by multiplex ligation-dependent probe amplification (MLPA). Sequence analysis and restriction assay were used to confirm the results. In addition, an analysis of a STR located in intron 1 of the OA1 gene (OA-CA) was performed.

Results:  The father of the proband presented with nystagmus, a feature consistent with XLOA. Mutation screening by multiplex ligation-dependent probe amplification and sequence analysis of the exon 2 of the OA1 gene led to the identification of the novel p.Glu129fsX35 (g.5815delA) mutation in two affected males and four carrier females. Three relatives were found to be non-mutated. The deletion detected resulted in a truncated protein 35 codons downstream and generated a new restriction site for the XcmI endonuclease. Additionally, microsatellite analysis showed co-segregation with the disease in the family.

Conclusions:  A novel deletion in the OA1 gene was identified in a Spanish family with ocular albinism. The mutation detected is likely a loss-of-function alteration. To the best of our knowledge, we describe the first Spanish family known to present with XLOA due to mutations in the OA1 gene.

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