扩大视网膜营养不良的临床、等位基因和基因座异质性。
Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.
作者信息
Patel Nisha, Aldahmesh Mohammed A, Alkuraya Hisham, Anazi Shamsa, Alsharif Hadeel, Khan Arif O, Sunker Asma, Al-Mohsen Saleh, Abboud Emad B, Nowilaty Sawsan R, Alowain Mohammed, Al-Zaidan Hamad, Al-Saud Bandar, Alasmari Ali, Abdel-Salam Ghada M H, Abouelhoda Mohamed, Abdulwahab Firdous M, Ibrahim Niema, Naim Ewa, Al-Younes Banan, E AlMostafa Abeer, AlIssa Abdulelah, Hashem Mais, Buzovetsky Olga, Xiong Yong, Monies Dorota, Altassan Nada, Shaheen Ranad, Al-Hazzaa Selwa A F, Alkuraya Fowzan S
机构信息
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Department of Ophthalmology, College of Medicine, Al-Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
出版信息
Genet Med. 2016 Jun;18(6):554-62. doi: 10.1038/gim.2015.127. Epub 2015 Sep 10.
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.Genet Med 18 6, 554-562.
目的
视网膜营养不良（RD）是视网膜的异质性遗传性疾病，通常具有进行性。本研究的目的是对一大群RD患者进行临床和分子特征分析。
方法
我们开发了一种新一代测序检测方法，可同时对已知的RD基因进行测序。我们还对在该检测中呈阴性的家族性和综合征性RD患者进行了定位研究和外显子组测序。
结果
我们的检测在292个接受检测的RD家族中，超过60%鉴定出可能的致病突变。对检测呈阴性的所有162例家族性RD患者进行的定位研究，在2号染色体上确定了两个新的疾病位点：25,550,180 - 28,794,007和16号染色体上的59,225,000 - 72,511,000。全外显子组测序分别揭示可能的候选基因是AGBL5和CDH16。我们还对阴性综合征性RD病例进行了外显子组测序，在一个黏多糖贮积症与RD新组合的家族中，鉴定出GNS中的一个新的纯合截短突变。此外，我们在一个患有视网膜色素变性和低丙种球蛋白血症明显新综合征的家族中，鉴定出DNAJC17中的一个纯合截短突变。
结论
我们的研究扩展了已知RD基因的临床和等位基因谱，并揭示AGBL5、CDH16和DNAJC17为新的疾病候选基因。《遗传医学》18卷6期，554 - 562页。
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