title: A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration).
abstract: Sveinsson's chorioretinal atrophy (SCRA), also referred to as helicoid peripapillary chorioretinal degeneration or atrophia areata, 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 an 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.
authors.affiliation: deCODE Genetics, IS-101 Reykjavik, Iceland. ragnheidur.fossdal@decode.is
authors.forename: Ragnheidur
authors.initials: R
authors.lastname: Fossdal
authors.forename: Fridbert
authors.initials: F
authors.lastname: Jonasson
authors.forename: Gudlaug T
authors.initials: GT
authors.lastname: Kristjansdottir
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Shyamali
authors.initials: S
authors.lastname: Gosh
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000483:Alleles; D000595:Amino Acid Sequence; D001665:Binding Sites; D015862:Choroid Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007055:Iceland; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010750:Phosphoproteins / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human