A rare homozygous rhodopsin splice-site mutation: the issue of when and whether to offer presymptomatic testing
A rare homozygous rhodopsin splice-site mutation: the issue of when and whether to offer presymptomatic testing
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DOI：
10.1076/opge.24.4.225.17235
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发表时间：
2003-01
影响因子：
1.2
通讯作者：
J. Greenberg;L. Roberts;R. Ramesar
中科院分区：
文献类型：
--
作者：
J. Greenberg;L. Roberts;R. Ramesar
在视网膜色素变性（RP）患者中确定了与疾病相关的视紫红质突变后，问题是要解决是否向有风险的家庭成员提供基因检测的问题。采用单链构象多态性分析和DNA测序技术，对1个南非（SA）家族的2名成员（其中1名为RP患者）和54名无血缘关系的SA RP患者进行了研究，发现先证者的视紫红质基因第4外显子内含子-外显子边界存在一种罕见的纯合突变。他的一个兄弟姐妹被发现是相同突变的杂合子。在54例无关的SA RP患者中未检测到突变，其中11例为散发病例。据报道，这种突变的杂合子携带者中RP的发生率较低;然而，过去还不清楚这种突变是否对单拷贝或双拷贝产生影响。据我们所知，这是第一次在受影响的个体中报告这种突变为纯合子，从而解决了这个问题并确认它是一种隐性疾病相关突变。这也是第一个常染色体隐性遗传RP疾病引起的视紫红质突变，已确定在南部非洲。对扩展家系的分析表明，该突变的专性杂合子携带者，在成年早期没有明显的视力障碍迹象。潜在的杂合子携带者应在何种程度上追求和临床检查进行了讨论，并解决了是否告知这些分子结果的家庭的问题。
Having identified a disease-associated rhodopsin mutation in a patient with retinitis pigmentosa (RP), the issue is to address the question of whether to offer genetic testing to at-risk family members. Two members of a South African (SA) family, one of whom suffers from RP, as well as 54 unrelated SA RP patients from the same population group were investigated using single-stranded conformational polymorphism analysis followed by DNA sequencing.A rare homozygous mutation at the intron-exon boundary of exon 4 in the rhodopsin gene was identified in the proband. One of his siblings was found to be heterozygous for the same mutation. The mutation was not detected in the 54 unrelated SA RP patients examined,11 of whom were sporadic cases. A low incidence of RP amongst heterozygous carriers of this mutation has been reported; however, in the past it has been unclear whether the mutation has an effect in single copy or dual copy. To the best of our knowledge, this is the first time that this mutation has been reported as homozygous in an affected individual, thereby resolving the issue and confirming that it is a recessive disease-associated mutation. This is also the first autosomal recessive RP disease-causing rhodopsin mutation that has been identified in Southern Africa. Analysis of the extended pedigree indicated obligate heterozygous carriers of the mutation, without obvious signs of visual impairment in early adulthood. The extent to which potential heterozygous carriers should be pursued and clinically examined is discussed and the question is addressed as to whether to inform the family of these molecular findings.