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RDS/peripherin gene mutations are frequent causes of central retinal dystrophies
S Kohl1, M Christ-Adler, E Apfelstedt-Sylla
1Universitäts-Augenklinik Tübingen, Germany.
Abstract:
Patients from 76 independent families with various forms of mostly central retinal dystrophies were screened for mutations in the RDS/peripherin gene by means of SSCP analysis and direct DNA sequencing. Two nonsense mutations (Gln239ter, Tyr285ter), five missense mutations (Arg172Trp, Lys197Glu, Gly208Asp, Trp246Arg, Ser289Leu), and one single base insertion (Gly208insG), heterozygous in all cases, were detected. Only one of these mutations, Arg172Trp, has been reported previously. Cosegregation of the mutation with the disease phenotype could be established in selected families. Other missense mutations were excluded from a panel of 55-75 control subjects. The patients showed remarkable variation in phenotype and disease expression not only between cases with different mutations but also between affected members of the same family. This study indicates that RDS/peripherin mutations are a frequent cause of various types of central retinal dystrophies and that the RDS/peripherin gene exhibits a broad spectrum of allelic mutations. Comparative analysis of known mutations allowed us to hypothesise that the deleterious effect of RDS/peripherin gene mutations is the result of different molecular mechanisms.
Insights
Mutations in the RDS/peripherin gene are a common cause of central retinal dystrophies. These genetic variations lead to diverse disease presentations, even within families.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Central retinal dystrophies encompass a group of inherited eye diseases affecting vision.
- The RDS/peripherin gene is implicated in retinal function and integrity.
Purpose of the Study:
- To identify mutations in the RDS/peripherin gene in patients with central retinal dystrophies.
- To analyze the spectrum of RDS/peripherin mutations and their correlation with disease phenotypes.
Main Methods:
- Screening of 76 families for RDS/peripherin gene mutations using Single-Strand Conformation Polymorphism (SSCP) analysis and direct DNA sequencing.
- Cosegregation analysis to confirm the link between mutations and disease in affected families.
- Control group analysis to validate identified mutations.
Main Results:
- Detection of eight heterozygous RDS/peripherin mutations: two nonsense (Gln239ter, Tyr285ter), five missense (Arg172Trp, Lys197Glu, Gly208Asp, Trp246Arg, Ser289Leu), and one insertion (Gly208insG).
- Only the Arg172Trp mutation was previously reported; others were novel.
- Significant phenotypic variability observed among patients, irrespective of mutation type or family.
- Exclusion of missense mutations in control subjects.
Conclusions:
- RDS/peripherin gene mutations are a frequent cause of diverse central retinal dystrophies.
- The RDS/peripherin gene displays a wide array of allelic mutations.
- Different molecular mechanisms likely underlie the effects of RDS/peripherin gene mutations.