Universität zu Köln

Brandl, Caroline ORCID: 0000-0001-8223-6137, Schulz, Heidi L., Issa, Peter Charbel ORCID: 0000-0002-0351-6673, Birtel, Johannes, Bergholz, Richard, Lange, Clemens, Dahlke, Claudia, Zobor, Ditta, Weber, Bernhard H. F. and Stoehr, Heidi (2017). Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions. Genes, 8 (7). BASEL: MDPI. ISSN 2073-4425

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brandl, Caroline UNSPECIFIED orcid.org/0000-0001-8223-6137 UNSPECIFIED Schulz, Heidi L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Issa, Peter Charbel UNSPECIFIED orcid.org/0000-0002-0351-6673 UNSPECIFIED Birtel, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergholz, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Lange, Clemens UNSPECIFIED UNSPECIFIED UNSPECIFIED Dahlke, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zobor, Ditta UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Bernhard H. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Heidi UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225501
DOI:	10.3390/genes8070170
Journal or Publication Title:	Genes
Volume:	8
Number:	7
Date:	2017
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4425
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETINITIS-PIGMENTOSA; DYSTROPHY; PROTEIN Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22550