id,collection,dc.contributor.author,dc.date.accessioned,dc.date.available,dc.date.issued,dc.description.abstract[en],dc.format.extent,dc.identifier.uri,dc.language,dc.rights.uri,dc.subject,dc.subject.ddc,dc.title,dc.type,dcterms.accessRights.openaire,dcterms.bibliographicCitation,dcterms.bibliographicCitation.doi,dcterms.bibliographicCitation.url,dcterms.isPartOf.issn,refubium.affiliation[de],refubium.mycore.derivateId,refubium.mycore.fudocsId,refubium.note.author,refubium.resourceType.isindependentpub "484de8d7-5006-4324-a57c-bf3f6601b67a","fub188/15","Brandl, Caroline||Schulz, Heidi L.||Issa, Peter Charbel||Birtel, Johannes||Bergholz, Richard||Lange, Clemens||Dahlke, Claudia||Zobor, Ditta||Weber, Bernhard H. F.||Stöhr, Heidi","2018-06-08T10:30:57Z","2017-10-13T12:36:23.343Z","2017","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.","14 Seiten","https://refubium.fu-berlin.de/handle/fub188/20574||http://dx.doi.org/10.17169/refubium-23875","eng","http://creativecommons.org/licenses/by/4.0/","vitelliform macular dystrophy||IMPG1||IMPG2||interphotoreceptor matrix||optical coherence tomography","600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit","Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions","Wissenschaftlicher Artikel","open access","Genes. - 8 (2017), 7, Artikel Nr. 170","10.3390/genes8070170","http://doi.org/10.3390/genes8070170","2073-4425","Charité - Universitätsmedizin Berlin","FUDOCS_derivate_000000008985","FUDOCS_document_000000028311","Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.","no"