Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies

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 Inherite d Eye Diseases (LMDIED) at the University of Texas Houston Health Science C enter 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 s equencing of five genes (rhodopsin, peripherin/RDS, RP1, CRX, and AIPL1) id entified the disease-causing mutation in approximately one-third of subject s with autosomal dominant retinitis pigmentosa (adRP) or with autosomal dom inant cone rod dystrophy (adCORD). In addition, the causative mutation was identified in 15% of subjects with Leber congenital amaurosis (LCA), Overal l, we report identification of the causative mutation in 105 of 506 (21%) o f unrelated subjects (probands) tested; we report five previously unreporte d mutations in rhodopsin, two in peripherin/RDS, and one previously unrepor ted 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 estimat ing the frequency of specific mutations and in selecting individuals and fa milies for mutation-specific studies. Hum Mutat 17:42-51, 2001, (C) 2001 Wi ley-Liss, Inc.