A novel nonsense mutation in Rhodopsin gene in two Indonesian Families with Autosomal Recessive Retinitis Pigmentosa

作者：Kartasasmita Arief^*; Fujiki Keiko; Iskandar Erwin; Sovani Iwan; Fujimaki Takuro; Murakami Akira

来源：Ophthalmic Genetics, 2011, 32(1): 57-63.

DOI：10.3109/13816810.2010.535892

• Rhodopsin
• autosomal recessive
• retinitis pigmentosa
• nonsense mutation

Purpose: To report a novel, identical nonsense mutation in the rhodopsin (RHO) gene in two Indonesian families with autosomal recessive retinitis pigmentosa (arRP).
Methods: Mutation screening for the RHO gene was performed in 38 unrelated patients with retinitis pigmentosa (RP) by direct sequencing. Clinical features were also characterized, through complete ophthalmologic examination. Family members of RP patients testing positive for the RHO gene were subjected to genetic and clinical examination. To assess the founder effect in the two families, haplotype analysis also was performed.
Results: A novel homozygous nonsense mutation was detected in two patients by a G to A transition at nucleotide position 482 in exon 2 of the RHO gene, resulting in substitution of a tryptophan-to-stop at codon 161 (c.482G > A, p.W161X). Examination of family members of these 2 patients showed that the affected members were homozygous and unaffected carriers were heterozygous for the p.W161X mutation. Haplotype analysis revealed that members of the two families carried the same disease-associated variants in markers (IVS1 RHO and D3S2322). No p.W161X mutations were detected in 45 normal Indonesian subjects, nor were any mutations detected in exons 1--5 of the RHO gene in the remaining 36 RP patients.
Conclusion: We detected a novel, recessive nonsense mutation (p.W161X) in the RHO gene of two families through mutation screening of RHO in 38 Indonesian RP patients. Haplotype analysis suggested that p.W161X was the founder mutation.

• 出版日期2011-3