A novel TEAD1 mutation is the causative allele in Sveinsson's Chorioretinal Atrophy (helicoid peripapillary chorioretinal degeneration)

Sveinsson's Chorioretinal Atrophy (SCRA) also referred to as Helicoid Peripapillary Chorioretinal Degeneration (HPCD) or Atrophia Areata (AA) is an autosomal dominant eye disease, characterized by symmetrical lesions radiating from the optic disc involving the retina and the choroid. Genome wid...

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Bibliographic Details
Published in:Human Molecular Genetics
Main Authors: Fossdal, Ragnheidur, Jonasson, Fridbert, Kristjansdottir, Gudlaug Thora, Kong, Augustine, Stefansson, Hreinn, Gosh, Shyamali, Gulcher, Jeffrey R., Stefansson, Kari
Format: Text
Language:English
Published: Oxford University Press 2004
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Online Access:http://hmg.oxfordjournals.org/cgi/content/short/ddh106v1
https://doi.org/10.1093/hmg/ddh106
Description
Summary:Sveinsson's Chorioretinal Atrophy (SCRA) also referred to as Helicoid Peripapillary Chorioretinal Degeneration (HPCD) or Atrophia Areata (AA) is an autosomal dominant eye disease, characterized by symmetrical lesions radiating from the optic disc involving the retina and the choroid. Genome wide linkage analysis mapped the SCRA gene to chromosome 11p15 in 81 patients from a large founder pedigree in Iceland. The parametric LOD score obtained was 18.9 using autosomal dominant model with high penetrance. Crossover analysis of the linkage region with 51 markers, identified a 593 kb segment shared by all patients. Sequencing exons of the only gene in this interval, the transcriptional enhancer TEAD1 , revealed a novel missense mutation (Y421H) carried by all patients and none of the 502 controls. The mutation is in a conserved amino acid sequence in the C terminal of the protein, a potential binding site for YAP65 one of TEAD1's cofactors that is expressed in human retina as well as TEAD1 based on RT-PCR experiments. Therefore, we conclude that the mutation in the TEAD1 gene is the cause of Sveinsson's Chorioretinal Atrophy.