Whole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of Retinitis Pigmentosa Accompanied by Pseudocoloboma.
Whole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of Retinitis Pigmentosa Accompanied by Pseudocoloboma.
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DOI：
10.1016/j.ophtha.2017.03.010
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发表时间：
2017-07
期刊：
影响因子：
13.7
通讯作者：
Cremers FPM
中科院分区：
文献类型：
--
作者：
Pierrache LHM;Kimchi A;Ratnapriya R;Roberts L;Astuti GDN;Obolensky A;Beryozkin A;Tjon-Fo-Sang MJH;Schuil J;Klaver CCW;Bongers EMHF;Haer-Wigman L;Schalij N;Breuning MH;Fischer GM;Banin E;Ramesar RS;Swaroop A;van den Born LI;Sharon D;Cremers FPM
目的探讨4个常染色体隐性遗传性视网膜色素变性（arRP）家系的遗传病因及表型特征。案例系列。来自4个无亲缘关系的arRP家系的7例患者，其中3例为双侧早发性黄斑假性缺损。我们对5个先证者和4个不相关家族的2个未受影响的家族成员进行了纯合性定位和全外显子组测序（WES）。随后，在其他家庭成员中进行桑格测序和分离分析。我们回顾了携带IDH 3A变体的个体的病史，并进行了额外的眼科检查，包括全视野视网膜电图（ffERG），眼底照相，眼底自发荧光成像和光学相干断层扫描。IDH 3A变体、诊断时的年龄、视力、眼底外观、视野、ffERG、眼底自发荧光和OCT结果。我们在四个不相关的家族中鉴定了IDH 3A的七种不同变体，即五种错义变体，一种无义变体和一种移码变体。所有受试者都在生命早期出现症状，从夜盲症到视力下降，并在1岁至11岁之间被诊断。4名具有双等位基因IDH 3A变体的受试者显示典型的arRP表型，3名受试者被诊断患有arRP和黄斑假性缺损。IDH 3A变体被鉴定为典型arRP的新原因，在一些与黄斑假性缺损相关的个体中。我们在携带相同复合杂合变体的两个兄弟姐妹中观察到两种表型，这可以通过可变疾病表达来解释，并且在断言基因型-表型相关性时需要谨慎。
To identify the genetic cause and describe the phenotype in four families with autosomal recessive retinitis pigmentosa (arRP) that can be associated with pseudocoloboma. Case series. Seven patients from four unrelated families with arRP of which three patients had bilateral early-onset macular pseudocoloboma. We performed homozygosity mapping and whole-exome sequencing (WES) in five probands and two unaffected family members of four unrelated families. Subsequently, Sanger sequencing and segregation analysis were done in additional family members. We reviewed the medical history of individuals carrying IDH3A variants and performed additional ophthalmic examinations, including full-field electroretinography (ffERG), fundus photography, fundus autofluorescence imaging and optical coherence tomography. IDH3A variants, age at diagnosis, visual acuity, fundus appearance, visual field, ffERG, fundus autofluorescence and OCT findings. We identified seven different variants in IDH3A in four unrelated families, i.e. five missense, one nonsense and one frameshift variant. All subjects developed symptoms early in life ranging from night blindness to decreased visual acuity and were diagnosed between the ages of one and 11 years. Four subjects with biallelic IDH3A variants displayed a typical arRP phenotype and three subjects were diagnosed with arRP and pseudocoloboma of the macula. IDH3A variants were identified as a novel cause of typical arRP, in some individuals associated with macular pseudocoloboma. We observed both phenotypes in two siblings carrying the same compound heterozygous variants, which could be explained by variable disease expression and warrants caution when making assertions about genotype-phenotype correlations.
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影响因子：
30.8
作者：
Falk, Marni J.;Zhang, Qi;Nakamaru-Ogiso, Eiko;Kannabiran, Chitra;Fonseca-Kelly, Zoe;Chakarova, Christina;Audo, Isabelle;Mackay, Donna S.;Zeitz, Christina;Borman, Arundhati Dev;Staniszewska, Magdalena;Shukla, Rachna;Palavalli, Lakshmi;Mohand-Said, Saddek;Waseem, Naushin H.;Jalali, Subhadra;Perin, Juan C.;Place, Emily;Ostrovsky, Julian;Xiao, Rui;Bhattacharya, Shomi S.;Consugar, Mark;Webster, Andrew R.;Sahel, Jose-Alain;Moore, Anthony T.;Berson, Eliot L.;Liu, Qin;Gai, Xiaowu;Pierce, Eric A.
通讯作者：
Pierce, Eric A.
影响因子：
4
作者：
Ajmal, Muhammad;Khan, Muhammad Imran;Cremers, Frans P. M.
通讯作者：
Cremers, Frans P. M.
影响因子：
4.4
作者：
Martínez-Gimeno, M;Gamundi, MJ;Carballo, M
通讯作者：
Carballo, M
影响因子：
8.8
作者：
Patel, Nisha;Aldahmesh, Mohammed A.;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.
影响因子：
4.1
作者：
KIM, YO;OH, IU;HUH, TL
通讯作者：
HUH, TL