The mutation p.E113K in the Schiff base counterion of rhodopsin is associated with two distinct retinal phenotypes within the same family
| Autor: | Charlotte Reiff, Marta Owczarek-Lipska, Georg Spital, Carsten Röger, Hebke Hinz, Christoph Jüschke, Holger Thiele, Janine Altmüller, Peter Nürnberg, Romain Da Costa, John Neidhardt |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Aged 80 and over Male Heterozygote Rhodopsin DNA Mutational Analysis Mutation Missense Sequence Analysis DNA Middle Aged Article Pedigree Phenotype Amino Acid Substitution Night Blindness Case-Control Studies Medicine and health Humans Female Amino Acid Sequence Retinitis Pigmentosa Schiff Bases |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The diagnoses of retinitis pigmentosa (RP) and stationary night blindness (CSNB) are two distinct clinical entities belonging to a group of clinically and genetically heterogeneous retinal diseases. The current study focused on the identification of causative mutations in the RP-affected index patient and in several members of the same family that reported a phenotype resembling CSNB. Ophthalmological examinations of the index patient confirmed a typical form of RP. In contrast, clinical characterizations and ERGs of another affected family member showed the Riggs-type CSNB lacking signs of RP. Applying whole exome sequencing we detected the non-synonymous substitution c.337G > A, p.E113 K in the rhodopsin (RHO) gene. The mutation co-segregated with the diseases. The identification of the pathogenic variant p.E113 K is the first description of a naturally-occurring mutation in the Schiff base counterion of RHO in human patients. The heterozygous mutation c.337G > A in exon 1 was confirmed in the index patient as well as in five CSNB-affected relatives. This pathogenic sequence change was excluded in a healthy family member and in 199 ethnically matched controls. Our findings suggest that a mutation in the biochemically well-characterized counterion p.E113 in RHO can be associated with RP or Riggs-type CSNB, even within the same family. |
| Databáze: | OpenAIRE |
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