PDF(Pubmed)
Abstract：
Mutations in the ALMS1 gene have been linked to isolated inherited retinal dystrophy or Alström syndrome. This report illustrates the unique pattern of ALMS1-associated diseases in a set of three simplex Saudi patients originating from unrelated consanguineous families. A detailed ophthalmological assessment was performed at the Department of Ophthalmology at King Saud University, Riyadh, Saudi Arabia. Next-generation sequencing vision panel revealed recessive ALMS1 mutations (reference sequence NM_015120). As a result, three distinct pathogenic ALMS1 mutations were identified; the first one is a nonsense mutation (c.8158C>T: p.R2720X) which has recently been identified in a Chinese patient, while the other two are known to have a founder effect in the Saudi population (the frameshift: C.848dupA: p.E283fs and the splicing: C.11870-2A>T: p.?). Clinically, a prominent nerve fiber layer was observed in the three studied patients with variable expectations of vessel attenuation. In addition, two of our patients observed unusual presentation of specific retinal pigment epithelium pigmentations in semi/halo-arrangement around the macula. Thus far, our report expands the phenotypic-genotypic spectrum of ALMS1-associated diseases and supports the principles of applying precision medicine in Saudi Arabia by utilizing the fact that common founder mutations were identified and unique phenotype was observed.
摘要：
ALMS1基因的突变与孤立的遗传性视网膜营养不良或Alström综合征有关。该报告说明了一组来自无关近亲家庭的三名单纯沙特患者中ALMS1相关疾病的独特模式。国王沙特大学眼科进行了详细的眼科评估，利雅得,沙特阿拉伯。下一代测序视觉小组显示隐性ALMS1突变(参考序列NM_015120)。因此,发现了三种不同的致病性ALMS1突变；第一种是无义突变（c.8158C>T：p.R2720X），最近在中国患者中发现了这种突变，而另外两个已知在沙特人口中具有创始人效应（移码：C.848dupA：p.E283fs和拼接：C.11870-2A>T：p.？）。临床上,在3名患者中观察到显著的神经纤维层,患者对血管衰减的期望值不同.此外,我们的两名患者观察到黄斑周围半/晕排列的特定视网膜色素上皮色素沉着的异常表现。到目前为止,我们的报告扩大了ALMS1相关疾病的表型-基因型谱,并利用发现了共同的创始人突变和观察到的独特表型这一事实,支持了在沙特阿拉伯应用精准医学的原则.
