Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies

TLDR

Inherited retinopathies affect about one in 2000 people worldwide and are genetically and phenotypically heterogeneous. The study estimates the prevalence of disease‑causing mutations in specific genes across retinitis pigmentosa and related disorders. The laboratory screened 506 unrelated probands using SSCA and direct sequencing of five genes (rhodopsin, peripherin/RDS, RP1, CRX, AIPL1) to identify pathogenic mutations. Mutations were found in 21% of probands overall, including 15% of Leber congenital amaurosis cases, one‑third of autosomal dominant retinitis pigmentosa or cone‑rod dystrophy cases, and five novel rhodopsin, two peripherin/RDS, and one novel CRX mutations. Hum Mutat 17:42–51, 2001; © 2001 Wiley‑Liss, Inc.

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.