Suppr超能文献

IQCB1 突变与莱伯先天性黑矇患者。

IQCB1 mutations in patients with leber congenital amaurosis.

机构信息

Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

出版信息

Invest Ophthalmol Vis Sci. 2011 Feb 11;52(2):834-9. doi: 10.1167/iovs.10-5221.

Abstract

PURPOSE

Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA.

METHODS

Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes.

RESULTS

In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal.

CONCLUSIONS

Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.

摘要

目的

莱伯先天性黑蒙(LCA)是一种遗传异质性疾病,迄今为止已发现 15 个基因,占 LCA 患者的∼70%。本研究旨在寻找新的 LCA 致病基因。

方法

利用高密度 SNP 微阵列对来自世界各地的 150 多名 LCA 患者进行全基因组纯合子作图,以鉴定新的致病基因。

结果

在 3 位孤立性 LCA 患者中,作者发现包含 IQCB1 基因的大片段纯合区域,该基因与先天性肾病型视网膜色素变性综合征(SLSN)有关,后者以肾单位肾病变和视网膜变性为特征。对这 3 位患者和随后的 222 位额外的 LCA 患者的 IQCB1 进行突变分析,发现 11 位被诊断为 LCA 的患者存在移码和无义突变。在重新检查患者的疾病状况时,发现其中 7 位患者发展为 SLSN,但有 4 位患者仍保持 LCA 的诊断,因为肾功能仍然正常。

结论

结果表明,IQCB1 突变患者的肾功能衰竭发病具有高度可变性,并且在没有肾单位肾病变的 LCA 患者中也发现了突变,这使得 IQCB1 成为 LCA 的一个新基因。然而,这些患者发生肾衰竭的风险很高,而在早期阶段,肾衰竭往往无法被识别,并可能导致因体液和电解质失衡而突然死亡。因此,建议对所有 LCA 患者进行 IQCB1 突变筛查,并更密切地监测他们的肾脏疾病。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验