Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies
Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies
复制标题
DOI：
10.1038/gim.2015.127
复制
发表时间：
2016-06-01
影响因子：
8.8
通讯作者：
Alkuraya, Fowzan S.
中科院分区：
文献类型：
--
作者：
Patel, Nisha;Aldahmesh, Mohammed A.;Alkuraya, Fowzan S.
目的：视网膜营养不良（RD）是异质性遗传性视网膜疾病，通常是进行性的。本研究的目的是临床和分子特征的RD patients.Methods大队列：我们已经开发出下一代测序检测！可以同时对已知的RD基因进行测序。我们还对家族性和！结果：我们的小组在292个检测的RD家族中确定了>60%的可能的因果突变。对所有162例家族性RD患者进行的定位研究在面板上检测为阴性，在Chr 2：25，550，180 - 28，794，007和Chr 16：59，225，000 - 72，511，000上确定了两个新的疾病基因座。全外显子组测序显示可能的候选分别为AGBL 5和CDH 16。我们还对阴性综合征型RD病例进行了外显子组测序，并在一个粘多糖样沉积症和RD新组合的家族中鉴定了一种新的GNS纯合截短突变。此外，我们确定了一个纯合的截断突变DNAJC 17在一个家庭显然是一个新的综合征的视网膜色素变性和hypogammaglobulinemia.Conclusion：我们的研究扩大了已知的RD基因的临床和等位基因谱，并揭示AGBL 5，CDH 16，和DNAJC 17;新的疾病候选人。
Purpose: Retinal dystrophies (RD) are heterogeneous hereditary disorders of the retina that are usually progressive in nature. The aim of this study was to clinically and molecularly characterize a large cohort of RD patients.Methods: We have developed a next-generation sequencing assay ! that allows known RD genes to be sequenced simultaneously. We also performed mapping studies and exome sequencing on familial and ! on syndromic RD patients who tested negative on the panel.Results: Our panel identified the likely causal mutation in >60% of the 292 RD families tested. Mapping studies on all 162 familial RD patients who tested negative on the panel identified two novel disease loci on Chr2:25,550,180-28,794,007 and Chr16:59,225,000-72,511,000. Whole-exome sequencing revealed the likely candidate as AGBL5 and CDH16, respectively. We also performed exome sequencing on negative syndromic RD cases and identified a novel homozygous truncating mutation in GNS in a family with the novel combination of mucopolysaccharidosis and RD. Moreover, we identified a homozygous truncating mutation in DNAJC17 in a family with an apparently novel syndrome of retinitis pigmentosa and hypogammaglobulinemia.Conclusion: Our study expands the clinical and allelic spectrum of known RD genes, and reveals AGBL5, CDH16, and DNAJC17 as; novel disease candidates.