Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies

Abstract

Inherited retinopathies are a genetically and phenotypically heterogeneous group of diseases affecting approximately one in 2000 individuals worldwide. For the past 10 years, the Laboratory for Molecular Diagnosis of Inherited Eye Diseases (LMDIED) at the University of Texas‐Houston Health Science Center has screened subjects ascertained in the United States and Canada for mutations in genes causing dominant and recessive autosomal retinopathies. A combination of single strand conformational analysis (SSCA) and direct sequencing of five genes (rhodopsin, peripherin/RDS, RP1, CRX, and AIPL1) identified the disease‐causing mutation in approximately one‐third of subjects with autosomal dominant retinitis pigmentosa (adRP) or with autosomal dominant cone‐rod dystrophy (adCORD). In addition, the causative mutation was identified in 15% of subjects with Leber congenital amaurosis (LCA). Overall, we report identification of the causative mutation in 105 of 506 (21%) of unrelated subjects (probands) tested; we report five previously unreported mutations in rhodopsin, two in peripherin/RDS, and one previously unreported mutation in the cone‐rod homeobox gene, CRX. Based on this large survey, the prevalence of disease‐causing mutations in each of these genes within specific disease categories is estimated. These data are useful in estimating the frequency of specific mutations and in selecting individuals and families for mutation‐specific studies. Hum Mutat 17:42–51, 2001. © 2001 Wiley‐Liss, Inc.

Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations

“…Moreover, P23H is, by far, the most common opsin mutation (8,68). We investigated the P23H-induced disease with modern techniques to improve understanding of its expression, retinal distribution, and rate of progression.…”

“…RP manifested predominantly by death of rod photoreceptor cells is a progressive disease characterized by night blindness that progresses to loss of peripheral vision and eventually all useful vision over decades (5). Of more than 100 mutant opsins associated with autosomal dominant RP (adRP), the most frequent mutation is P23H (6), accounting for ϳ10% of human cases (7,8).In vitro studies have shown that the P23H opsin associated with adRP is misfolded and retained in the ER (9 -12). Consequently, this protein is not transported to the cell membrane (12) but instead was degraded by the ubiquitin-proteosome system (13).…”

“…RP manifested predominantly by death of rod photoreceptor cells is a progressive disease characterized by night blindness that progresses to loss of peripheral vision and eventually all useful vision over decades (5). Of more than 100 mutant opsins associated with autosomal dominant RP (adRP), the most frequent mutation is P23H (6), accounting for ϳ10% of human cases (7,8).…”

A novel peripherin/RDS mutation resulting in a retinal dystrophy with phenotypic variation

“…3,4 To our knowledge, this is the first report of this three amino-acid deletion that interestingly causes a highly variable phenotype within the same family. In addition, it highlights choroidal neovascularisation as a potential complication.…”

Identifying Retinal Disease Genes: How Far Have We Come, How Far Do We Have to Go?

“…In fact, of the scores of mutations reported at each locus, typically 2 or 3 are much more prevalent than others. Focusing specifically on ADRP, Table 3 lists pathogenic mutations which are found in multiple, unrelated families (Sohocki et al 2001,Bowne et al 1999,2002. (Similar findings apply to other forms of inherited retinal disease.)…”