Genes 2017, 8(7), 170; https://doi.org/10.3390/genes8070170
Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions
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Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Regensburg, 93053 Regensburg, Germany
2
Institut für Humangenetik, Universität Regensburg, 93053 Regensburg, Germany
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Lehrstuhl für Genetische Epidemiologie, Universität Regensburg, 93053 Regensburg, Germany
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Department of Ophthalmology, University of Bonn, 53113 Bonn, Germany
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Oxford Eye Hospital, OUH NHS Foundation Trust and the Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3BD, UK
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Klinik für Augenheilkunde, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany
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Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert Ludwigs Universität Freiburg, 79085 Freiburg, Germany
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Klinik für Augenheilkunde, Universitätsklinikum Köln, 50937 Köln, Germany
9
Forschungsinstitut für Augenheilkunde, Universitätsklinikum Tübingen, 72076 Tübingen, Germany
*
Author to whom correspondence should be addressed.
Received: 19 May 2017 / Revised: 20 June 2017 / Accepted: 20 June 2017 / Published: 23 June 2017
(This article belongs to the Special Issue Inherited Retinal Disease: Novel Candidate Genes, Genotype–Phenotype Correlations and Inheritance Models)
Abstract
A significant portion of patients diagnosed with vitelliform macular dystrophy (VMD) do not carry causative mutations in the classic VMD genes BEST1 or PRPH2. We therefore performed a mutational screen in a cohort of 106 BEST1/PRPH2-negative VMD patients in two genes encoding secreted interphotoreceptor matrix proteoglycans-1 and -2 (IMPG1 and IMPG2). We identified two novel mutations in IMPG1 in two simplex VMD cases with disease onset in their early childhood, a heterozygous p.(Leu238Pro) missense mutation and a homozygous c.807 + 5G > A splice site mutation. The latter induced partial skipping of exon 7 of IMPG1 in an in vitro splicing assay. Furthermore, we found heterozygous mutations including three stop [p.(Glu226*), p.(Ser522*), p.(Gln856*)] and five missense mutations [p.(Ala243Pro), p.(Gly1008Asp), p.(Phe1016Ser), p.(Tyr1042Cys), p.(Cys1077Phe)] in the IMPG2 gene, one of them, p.(Cys1077Phe), previously associated with VMD. Asymptomatic carriers of the p.(Ala243Pro) and p.(Cys1077Phe) mutations show subtle foveal irregularities that could characterize a subclinical stage of disease. Taken together, our results provide further evidence for an involvement of dominant and recessive mutations in IMPG1 and IMPG2 in VMD pathology. There is a remarkable similarity in the clinical appearance of mutation carriers, presenting with bilateral, central, dome-shaped foveal accumulation of yellowish material with preserved integrity of the retinal pigment epithelium (RPE). Clinical symptoms tend to be more severe for IMPG1 mutations. View Full-TextKeywords:
vitelliform macular dystrophy; IMPG1; IMPG2; interphotoreceptor matrix; optical coherence tomography
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Brandl, C.; Schulz, H.L.; Charbel Issa, P.; Birtel, J.; Bergholz, R.; Lange, C.; Dahlke, C.; Zobor, D.; Weber, B.H.F.; Stöhr, H. Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions. Genes 2017, 8, 170.
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