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