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Genomewide Homozygosity Mapping and Molecular Analysis of a Candidate Gene Located on 22q13 (Fibulin-1) in a Previously Undescribed Vitreoretinal Dystrophy
Maike Weigell-Weber, MD;
Gian-Marco Sarra, MD;
Dieter Kotzot, MD;
Lodewijk Sandkuijl, PhD;
Elmar Messmer, MD;
Martin Hergersberg, PhD
Arch Ophthalmol. 2003;121:1184-1188.
Objectives To localize the gene that causes an autosomal recessively inherited vitreoretinal dystrophy that has not been described, to our knowledge, and to analyze a candidate gene mapped to 22q13 (fibulin-1 [FBLN1]).
Methods Homozygosity mapping with 500 microsatellite markers spread over the whole genome (mean distance, 7.2 centimorgans [cM]) and mutation analysis of the complete coding region of FBLN1.
Results Homozygosity for all analyzed markers was found in the 4 affected siblings in a region on chromosome 22 encompassing 12 cM from D22S444 (centromeric) to D22S1170 (telomeric). Lod scores were between 0.017 and 2.36 (theta = 0). A mutation analysis of the complete coding region of FBLN1, which encodes interacting extracellular matrix proteins, revealed 4 previously undescribed single nucleotide polymorphisms.
Conclusions A genomewide homozygosity mapping analysis supported the hypothesis that the gene responsible for a unique vitreoretinal dystrophy is located on chromosome 22q13. No obviously pathogenic mutation was found in the candidate gene, FBLN1.
From the Institute of Medical Genetics, University of Zurich (Drs Weigell-Weber and Hergersberg); Department of Ophthalmology, University Hospital Zurich, Frauenklinikstr (Drs Sarra and Messmer), Zurich, Switzerland; the Institute of Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, Austria (Dr Kotzot); Department of Medical Statistics, Leiden, the Netherlands (Dr Sandkuijl). Dr Sarra is currently affiliated with the Department of Ophthalmology, Inselspital, Berne, Switzerland; Dr Messmer, with Stadtspital Triemli, Zurich; and Dr Hergersberg, with Zentrum für Labormedizin, Aarau, Switzerland. The authors have no relevant financial interest in this article.
Dr Sandkuijl is deceased.
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