Identification of a novel nonsense mutation in RP1 that causes autosomal recessive retinitis pigmentosa in an Indonesian family.
OBJECTIVE
The purpose of this study was to identify the underlying molecular genetic defect in an Indonesian family with three affected individuals who had received a diagnosis of retinitis pigmentosa (RP).


METHODS
Clinical evaluation of the family members included measuring visual acuity and fundoscopy, and assessing visual field and color vision. Genomic DNA of the three affected individuals was analyzed with Illumina 700k single nucleotide polymorphism (SNP) arrays, and homozygous regions were identified using PLINK software. Mutation analysis was performed with sequence analysis of the retinitis pigmentosa 1 (RP1) gene that resided in one of the homozygous regions. The frequency of the identified mutation in the Indonesian population was determined with TaqI restriction fragment length polymorphism analysis.


RESULTS
A novel homozygous nonsense mutation in exon 4 of the RP1 gene, c.1012C>T (p.R338*), was identified in the proband and her two affected sisters. Unaffected family members either carried two wild-type alleles or were heterozygous carriers of the mutation. The mutation was not present in 184 Indonesian control samples.


CONCLUSIONS
Most of the previously reported RP1 mutations are inherited in an autosomal dominant mode, and appear to cluster in exon 4. Here, we identified a novel homozygous p.R338* mutation in exon 4 of RP1, and speculate on the mutational mechanisms of different RP1 mutations underlying dominant and recessive RP.
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Anna M
AM
Siemiatkowska
Galuh D N
GD
Astuti
Kentar
K
Arimadyo
Anneke I
AI
den Hollander
Sultana M H
SM
Faradz
Frans P M
FP
Cremers
Rob W J
RW
Collin
D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007214:Indonesia; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D010375:Pedigree; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics*; D014792:Visual Acuity
D018389:Codon, Nonsense; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human