A novel nonsense mutation in Rhodopsin gene in two Indonesian Families with Autosomal Recessive Retinitis Pigmentosa
A novel nonsense mutation in Rhodopsin gene in two Indonesian Families with Autosomal Recessive Retinitis Pigmentosa
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DOI：
10.3109/13816810.2010.535892
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发表时间：
2011-03-01
影响因子：
1.2
通讯作者：
Murakami, Akira
中科院分区：
文献类型：
--
作者：
Kartasasmita, Arief;Fujiki, Keiko;Murakami, Akira
目的：报道两个印度尼西亚常染色体隐性视网膜色素变性（arRP）家族中紫红质（RHO）基因的一种新的、相同的无义突变。方法：对38例无亲缘关系的色素性视网膜炎（RP）患者进行RHO基因突变筛查。通过完整的眼科检查，也确定了临床特征。RHO基因检测阳性的RP患者的家庭成员进行遗传和临床检查。为了评估两个家族的奠基者效应，还进行了单倍型分析。结果：在两例患者中，通过RHO基因外显子2核苷酸位置482的G到A的过渡，检测到一种新的纯合无义突变，导致色氨酸在密码子161处被取代（c.482G > A, p.W161X）。对这2例患者的家庭成员进行检测，发现p.W161X突变的患病成员为纯合子，未患病的携带者为杂合子。单倍型分析显示，两个家族的成员携带相同的疾病相关变异标记（IVS1 RHO和D3S2322）。在45名印度尼西亚正常受试者中未检测到p.W161X突变，在其余36名RP患者中RHO基因外显子1- 5也未检测到任何突变。结论：通过对38例印度尼西亚RP患者的RHO基因进行突变筛查，在2个家族的RHO基因中检测到一种新的隐性无义突变（p.W161X）。单倍型分析表明p.W161X为始祖突变。
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.