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Autosomal dominant pericentral retinal dystrophy caused by a novel missense mutation in the TOPORS gene
Author(s) -
Selmer Kaja Kristine,
Grøndahl Jan,
Riise Ruth,
Brandal Kristin,
Braaten Øivind,
Bragadottir Ragnheidur,
Undlien Dag Erik
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.01465.x
Subject(s) - missense mutation , genetics , dystrophy , mutation , gene , retinal , biology , ophthalmology , medicine
. Purpose: This study aimed to identify the genetic cause of autosomal dominant pericentral retinal dystrophy (adPRD) in a large Norwegian family with 35 affected members. Methods: The family was characterized by clinical ophthalmological examination along with fundus photography, dark adaptometry and electroretinography. We performed a genome‐wide linkage analysis followed by sequencing of a candidate gene to identify the mutation causing the disease. Results: The ophthalmological examinations revealed an atypical form of retinitis pigmentosa (RP), which we prefer to call adPRD. Compared with classical RP, this phenotype has a favourable prognosis. Linkage analysis showed a linkage peak covering the most recently reported adRP gene TOPORS . This gene was sequenced in 19 family members and a novel missense mutation, c.1205a>c, resulting in an amino acid substitution p.Q402P, was detected in all affected members. The mutation showed complete co‐segregation with the disease in this family, with a LOD score of 7.3. It is located in a highly conserved region and alignment with the appropriate DNA sequence from other species shows complete conservation of this amino acid. The mutation was not detected in 207 healthy, unrelated controls of Norwegian origin. Conclusions: We present a novel mutation in the TOPORS gene co‐segregating with a distinct phenotype of adPRD in a large Norwegian family.