1. Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions.
- Author
-
Brandl, Caroline, Schulz, Heidi L., Issa, Peter Charbel, Birtel, Johannes, Bergholz, Richard, Lange, Clemens, Dahlke, Claudia, Zobor, Ditta, Weber, Bernhard H. F., and Stöhr, Heidi
- Subjects
- *
INTERPHOTORECEPTOR matrix , *SIALOGLYCOPROTEINS , *PROTEOGLYCANS , *EYE diseases , *RHODOPSIN , *OPTICAL coherence tomography , *PATIENTS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF