Multimodal imaging and genetic characteristics of Chinese patients with USH2A-associated nonsyndromic retinitis pigmentosa.
Multimodal imaging and genetic characteristics of Chinese patients with USH2A-associated nonsyndromic retinitis pigmentosa.
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中国USH2A相关非综合征性视网膜色素变性患者的多模态成像和遗传特征
DOI：
10.1002/mgg3.1479
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发表时间：
2020-11
影响因子：
2
通讯作者：
Yu S
中科院分区：
文献类型：
--
作者：
Chen C;Sun Q;Gu M;Qian T;Luo D;Liu K;Xu X;Yu S
为了确定五个中国家庭中与非综合征性色素性视网膜炎 (RP) 相关的 USH2A 突变的临床特征和分子遗传背景，进行了一项回顾性横断面研究。从病历中提取详细病史和全面眼科检查的数据。通过全外显子组测序对基因组 DNA 进行测序。通过计算机分析评估致病性预测。基于I-Tasser软件显示了宽型和突变型USH2A蛋白的结构模型。超广角眼底成像显示黄斑保留的中心凹旁环具有独特的超自体荧光模式。检测到 10 个 USH2A 变异，包括 7 个错义突变、2 个剪接突变和 1 个插入突变。其中六种变体已被报道，其余四种是新的。在从头突变中，p.C931Y 和 p.G4489S 突变预计是有害的或可能具有破坏性； p.M4853V 突变被预测为中性或良性； IVS22+3A>G突变为剪接突变，可影响mRNA剪接，影响USH2A蛋白发夹结构的形成。我们的数据进一步证实，USH2A 蛋白在维持光感受器方面发挥着关键作用，并扩大了与中国患者非综合征性 RP 相关的 USH2A 突变谱。本研究利用全外显子组测序方法在非综合征型 RP 患者中发现了 USH2A 基因的新突变。携带 USH2A 突变的 RP 患者在超广角眼底自发荧光中具有独特的模式。
To determine the clinical characteristics and molecular genetic background responsible for USH2A mutations associated with nonsyndromic retinitis pigmentosa (RP) in five Chinese families, a retrospective cross‐sectional study was performed. Data on detailed history and comprehensive ophthalmological examinations were extracted from medical charts. Genomic DNA was sequenced by whole‐exome sequencing. The pathogenicity predictions were evaluated by in silico analysis. The structural modeling of the wide‐type and mutant USH2A proteins was displayed based on the I‐Tasser software. The ultra‐wide‐field fundus imaging showed a distinctive pattern of hyperautofluorescence in the parafoveal ring with macular sparing. Ten USH2A variants were detected, including seven missense mutations, two splicing mutations, and one insertion mutation. Six of these variants have already been reported, and the remaining four were novel. Of the de novo mutations, the p.C931Y and p.G4489S mutations were predicted to be deleterious or probably damaging; the p.M4853V mutation was predicted to be neutral or benign; and the IVS22+3A>G mutation was a splicing mutation that could influence mRNA splicing and affect the formation of the hairpin structure of the USH2A protein. Our data further confirm that USH2A protein plays a pivotal role in the maintenance of photoreceptors and expand the spectrum of USH2A mutations that are associated with nonsyndromic RP in Chinese patients. This study identified novel mutations of the USH2A gene using a whole‐exome sequencing approach in nonsyndromic RP patients. RP patients with USH2A mutations have a distinctive pattern in ultra‐wide‐field fundus autofluorescence.
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影响因子：
4.4
作者：
Jaijo, Teresa;Aller, Elena;Millan, Jose M.
通讯作者：
Millan, Jose M.
影响因子：
12.3
作者：
Ayuso C;Millan JM
通讯作者：
Millan JM
影响因子：
3.7
作者：
Oh, Jin Kyun;Lima de Carvalho, Jose Ronaldo, Jr.;Tsang, Stephen H.
通讯作者：
Tsang, Stephen H.
影响因子：
3.9
作者：
Neveling, Kornelia;Collin, Rob W. J.;Gilissen, Christian;van Huet, Ramon A. C.;Visser, Linda;Kwint, Michael P.;Gijsen, Sabine J.;Zonneveld, Marijke N.;Wieskamp, Nienke;de Ligt, Joep;Siemiatkowska, Anna M.;Hoefsloot, Lies H.;Buckley, Michael F.;Kellner, Ulrich;Branham, Kari E.;den Hollander, Anneke I.;Hoischen, Alexander;Hoyng, Carel;Klevering, B. Jeroen;van den Born, L. Ingeborgh;Veltman, Joris A.;Cremers, Frans P. M.;Scheffer, Hans
通讯作者：
Scheffer, Hans
DOI：
10.1038/ejhg.2014.283
发表时间：
2015-10
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Lenassi E;Vincent A;Li Z;Saihan Z;Coffey AJ;Steele-Stallard HB;Moore AT;Steel KP;Luxon LM;Héon E;Bitner-Glindzicz M;Webster AR
通讯作者：
Webster AR