The mutation p.E113K in the Schiff base counterion of rhodopsin is associated with two distinct retinal phenotypes within the same family.
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.
Eye Center, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Charlotte
C
Reiff
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Marta
M
Owczarek-Lipska
Department of Ophthalmology, St. Franziskus-Hospital, Münster, Germany.
Georg
G
Spital
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Carsten
C
Röger
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Hebke
H
Hinz
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Christoph
C
Jüschke
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
Holger
H
Thiele
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
Janine
J
Altmüller
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
Peter
P
Nürnberg
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Romain
R
Da Costa
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
John
J
Neidhardt
D000328:Adult; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009755:Night Blindness / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000000981:diagnostic imaging / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics*; D012545:Schiff Bases; D017422:Sequence Analysis, DNA
D012545:Schiff Bases; D012243:Rhodopsin