Kartasasmita Arief, Fujiki Keiko, Iskandar Erwin, Sovani Iwan, Fujimaki Takuro, Murakami Akira
Department of Ophthalmology, Faculty of Medicine, Padjadjaran University/Cicendo National Eye Hospital, Bandung, Indonesia.
Ophthalmic Genet. 2011 Mar;32(1):57-63. doi: 10.3109/13816810.2010.535892. Epub 2010 Dec 21.
To report a novel, identical nonsense mutation in the rhodopsin (RHO) gene in two Indonesian families with autosomal recessive retinitis pigmentosa (arRP).
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.
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.
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.
报告两个患有常染色体隐性视网膜色素变性（arRP）的印度尼西亚家庭中，视紫红质（RHO）基因存在一种新的相同无义突变。
通过直接测序对38名无关的视网膜色素变性（RP）患者进行RHO基因突变筛查。通过全面的眼科检查对临床特征进行了描述。对RHO基因检测呈阳性的RP患者家庭成员进行了基因和临床检查。为评估这两个家庭中的奠基者效应，还进行了单倍型分析。
在两名患者中检测到一种新的纯合无义突变，该突变发生在RHO基因第2外显子核苷酸位置482处，由G突变为A，导致密码子161处的色氨酸被替换为终止密码子（c.482G>A，p.W161X）。对这2名患者家庭成员的检查显示，受影响成员为该p.W161X突变的纯合子，未受影响的携带者为杂合子。单倍型分析显示，两个家庭的成员在标记物（IVS1 RHO和D3S2322）中携带相同的疾病相关变异。在45名正常印度尼西亚受试者中未检测到p.W161X突变，在其余36名RP患者的RHO基因第1-5外显子中也未检测到任何突变。
通过对38名印度尼西亚RP患者的RHO基因进行突变筛查，我们在两个家庭的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是奠基者突变。
