Two novel missense mutations in the peripherin/RDS gene in two unrelated French patients with autosomal dominant retinitis pigmentosa.
OBJECTIVE
To report the identification of two novel RDS mutations in the peripherin/RDS gene of two unrelated French patients affected by autosomal dominant retinitis pigmentosa (ADRP).


METHODS
Fifty-eight unrelated patients affected by ADRP were analyzed. Our diagnostic for RP were bilateral fundus involvement, concentric depression of the visual field and severe involvement on electroretinogram. Transmission of the trait was unambiguous. Our strategy was to analyze the coding sequence of the gene using a combination of single-strand conformation polymorphism (SSCP) and direct sequence analysis of the exons of the gene. Exons that displayed conformational polymorphisms were sequenced on an automated DNA sequencer.


RESULTS
The sequence analyses revealed two previously unreported missense mutations: Cys165Tyr and Phe211Leu in exons 1 and 2, respectively. None of the 70 controls analyzed carried these base changes. Cosegregation of the base substitution with the disease could be tested in both families presenting the Cys165Tyr and Phe211Leu mutations.


CONCLUSIONS
Several lines of evidence support the idea that these base substitutions are disease-causing mutations. To the best of our knowledge, no peripherin/RDS gene analysis has been previously reported in ADRP in France.
Service de Génétique I'Enfant INSERM-U-393 Hôpital des Enfants-Malades, Paris.
E H
EH
Souied
J M
JM
Rozet
S
S
Gerber
J L
JL
Dufier
G
G
Soubrane
G
G
Coscas
A
A
Munnich
J
J
Kaplan
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005602:France; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017422:Sequence Analysis, DNA
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D004247:DNA