Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.
Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.
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DOI：
10.1136/bjophthalmol-2018-312064
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
ProgStar Study Group
中科院分区：
文献类型：
--
作者：
Fujinami K;Strauss RW;Chiang JP;Audo IS;Bernstein PS;Birch DG;Bomotti SM;Cideciyan AV;Ervin AM;Marino MJ;Sahel JA;Mohand-Said S;Sunness JS;Traboulsi EI;West S;Wojciechowski R;Zrenner E;Michaelides M;Scholl HPN;ProgStar Study Group;ProgStar Study Group
描述国际多中心Stargardt病进展1（STGD 1）研究（ProgStar）入组队列的遗传特征，并根据等位基因频率确定地理差异。从美国和欧洲的9个中心招募了345名临床诊断为STGD 1并携带至少一种致病ABCA 4变体的参与者。审查了所有变体，并进行了计算机模拟分析，包括公共数据库中的等位基因频率和致病性预测。将具有多种可能致病性变异的参与者分为四个国家亚组（美国、英国、法国、德国），随后对每个流行等位基因的等位基因频率进行比较分析。在整个队列中确定了211种可能的致病性变体，包括错义（63%），剪接位点改变（18%），终止（9%）和其他。50种变体为新变体。在279例具有多种致病性变异的患者中，有139例（50%）检测到完全错义变异。这些具有多种致病性变体的患者的三种最普遍的变体是p.G1961E（15%）、p.G863A（7%）和c.5461-10 T>C（5%）。亚组分析显示，四个招募国家之间的9个变异的等位基因频率的统计学显着差异。在一个充分表征的队列中存在大量ABCA 4序列变体，包括50种新变体，从而进一步增加了STGD 1中独特的等位基因异质性。大约一半的队列仅含有错义变体，表明ProgStar队列的表型相对较轻。虽然三种最常见的变异体是常见的变异体，但各国之间的等位基因频率存在显着差异。
To describe the genetic characteristics of the cohort enrolled in the international multicentre progression of Stargardt disease 1 (STGD1) studies (ProgStar) and to determine geographic differences based on the allele frequency. 345 participants with a clinical diagnosis of STGD1 and harbouring at least one disease-causing ABCA4 variant were enrolled from 9 centres in the USA and Europe. All variants were reviewed and in silico analysis was performed including allele frequency in public databases and pathogenicity predictions. Participants with multiple likely pathogenic variants were classified into four national subgroups (USA, UK, France, Germany), with subsequent comparison analysis of the allele frequency for each prevalent allele. 211 likely pathogenic variants were identified in the total cohort, including missense (63%), splice site alteration (18%), stop (9%) and others. 50 variants were novel. Exclusively missense variants were detected in 139 (50%) of 279 patients with multiple pathogenic variants. The three most prevalent variants of these patients with multiple pathogenic variants were p.G1961E (15%), p.G863A (7%) and c.5461-10 T>C (5%). Subgroup analysis revealed a statistically significant difference between the four recruiting nations in the allele frequency of nine variants. There is a large spectrum of ABCA4 sequence variants, including 50 novel variants, in a well-characterised cohort thereby further adding to the unique allelic heterogeneity in STGD1. Approximately half of the cohort harbours missense variants only, indicating a relatively mild phenotype of the ProgStar cohort. There are significant differences in allele frequencies between nations, although the three most prevalent variants are shared as frequent variants.
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Stargardt病：临床特征，分子遗传学，动物模型和治疗选择。
DOI：
10.1136/bjophthalmol-2016-308823
发表时间：
2017-01
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Tanna P;Strauss RW;Fujinami K;Michaelides M
通讯作者：
Michaelides M
影响因子：
3.5
作者：
Braun TA;Mullins RF;Wagner AH;Andorf JL;Johnston RM;Bakall BB;Deluca AP;Fishman GA;Lam BL;Weleber RG;Cideciyan AV;Jacobson SG;Sheffield VC;Tucker BA;Stone EM
通讯作者：
Stone EM
影响因子：
13.7
作者：
Strauss, Rupert W.;Ho, Alex;Scholl, Hendrik P. N.
通讯作者：
Scholl, Hendrik P. N.
影响因子：
4.4
作者：
Fritsche, Lars G.;Fleckenstein, Monika;Weber, Bernhard H. F.
通讯作者：
Weber, Bernhard H. F.
影响因子：
4.4
作者：
Fakin, Ana;Robson, Anthony G.;Webster, Andrew R.
通讯作者：
Webster, Andrew R.