Discordant phenotypes in twins with infantile nystagmus.
Discordant phenotypes in twins with infantile nystagmus.
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DOI：
10.1038/s41598-021-82368-0
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发表时间：
2021-02-02
影响因子：
4.6
通讯作者：
Thomas MG
中科院分区：
文献类型：
--
作者：
Aamir A;Kuht HJ;McLean RJ;Maconachie GDE;Sheth V;Dawar B;Purohit R;Sylvius N;Hisaund M;Zubcov-Iwantscheff A;Proudlock FA;Gottlob I;Thomas MG
婴儿眼球震颤（IN）可能由白化病和FRMD 7突变等病因引起。IN患病率低，双胞胎IN罕见。虽然不一致的介绍以前已报告的IN，我们提出的第一次全面评估诊断不一致的单卵双胞胎。从2000多名患者中，我们发现了眼球震颤不一致的双胞胎和三胞胎。使用下一代测序，高分辨率红外瞳孔跟踪和光学相干断层扫描，我们的特点在基因型和表型的差异。包括单卵双胞胎（n = 1）、双卵双胞胎（n = 3）和三胞胎（n = 1）。同卵双胞胎有一致的TYR变异。在三联体中未鉴定出致病性变体。异卵双生子在TYR、OCA2和FRMD7中存在不一致的变异。一个未受影响的双胞胎表现出亚临床眼球震颤。在五个先证者中的四个中注意到黄斑中心凹发育不全（FH）。同卵双胞胎和三胞胎均显示FH。三个家系中至少有一个父母患有FH，但无眼球震颤。单用FH可能不足以引起眼球震颤。虽然视动反射通路发育停滞与IN有关，但不一致的双胞胎引发了有关发育差异在哪里出现的问题。因此，在未受影响的单合子中，遗传变异可能使眼部不稳定性易感，可变的表达性可能是观察到的不一致性的原因。
Infantile nystagmus (IN) may result from aetiologies including albinism and FRMD7 mutations. IN has low prevalence, and twins with IN are rare. Whilst discordant presentation has been previously reported for IN, we present for the first time the comprehensive assessment of diagnostically discordant monozygotic twins. From a cohort of over 2000 patients, we identified twins and triplets discordant for nystagmus. Using next-generation sequencing, high-resolution infra-red pupil tracking and optical coherence tomography, we characterised differences in genotype and phenotype. Monozygotic twins (n = 1), dizygotic twins (n = 3) and triplets (n = 1) were included. The monozygotic twins had concordant TYR variants. No causative variants were identified in the triplets. Dizygotic twins had discordant variants in TYR, OCA2 and FRMD7. One unaffected co-twin demonstrated sub-clinical nystagmus. Foveal hypoplasia (FH) was noted in four of five probands. Both co-twins of the monozygotic pair and triplets displayed FH. In three families, at least one parent had FH without nystagmus. FH alone may be insufficient to develop nystagmus. Whilst arrested optokinetic reflex pathway development is implicated in IN, discordant twins raise questions regarding where differences in development have arisen. In unaffected monozygotes therefore, genetic variants may predispose to oculomotor instability, with variable expressivity possibly responsible for the discordance observed.
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影响因子：
3.5
作者：
Thomas MG;Crosier M;Lindsay S;Kumar A;Araki M;Leroy BP;McLean RJ;Sheth V;Maconachie G;Thomas S;Moore AT;Gottlob I
通讯作者：
Gottlob I
影响因子：
13.7
作者：
Kruijt, Charlotte C.;de Wit, Gerard C.;van Genderen, Maria M.
通讯作者：
van Genderen, Maria M.
影响因子：
3.9
作者：
Simeonov, Dimitre R.;Wang, Xinjing;Wang, Chen;Sergeev, Yuri;Dolinska, Monika;Bower, Matthew;Fischer, Roxanne;Winer, David;Dubrovsky, Genia;Balog, Joan Z.;Huizing, Marjan;Hart, Rachel;Zein, Wadih M.;Gahl, William A.;Brooks, Brian P.;Adams, David R.
通讯作者：
Adams, David R.
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M
影响因子：
4.3
作者：
Nathan, Vaishnavi;Johansson, Peter A.;Hayward, Nicholas K.
通讯作者：
Hayward, Nicholas K.