Abnormal retinal development associated with FRMD7 mutations.
Abnormal retinal development associated with FRMD7 mutations.
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DOI：
10.1093/hmg/ddu122
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发表时间：
2014-08-01
影响因子：
3.5
通讯作者：
Gottlob I
中科院分区：
文献类型：
--
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
特发性婴儿眼球震颤（IIN）是一种遗传异质性疾病，通常与FRMD 7突变有关。由于视网膜的外观据报道是正常的基础上，传统的眼底摄影，IIN被假定为产生异常的皮质发育。为了确定传入视觉系统是否参与FRMD7突变，我们在人类胚胎和胎儿阶段（排卵后35天至受孕后9周）进行了原位杂交研究。我们显示了FRMD7在发育过程中的动态视网膜表达模式。我们观察到表达的外成神经细胞层，然后在内成神经细胞层，并在9周后的概念双层表达模式。在发育中的视柄和视盘内也观察到表达。我们确定了一个大的IIN患者队列（n = 100），并进行了序列分析，发现45例患者具有FRMD7突变。FRMD7突变患者使用超高分辨率光学相干断层扫描进行详细的视网膜成像研究。将断层图像与对照队列（n = 60）进行比较。FRMD7组的黄斑中心凹明显变浅（P < 0.0001）。视乳头形态异常，视乳头面积、视乳头杯面积、视乳头杯深度、视网膜神经纤维层厚度均明显减少（P < 0.0001）。这项研究首次表明，传入系统发育异常与FRMD7突变有关，可能是眼球震颤发生的重要病因。
Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at 9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.
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影响因子：
30.8
作者：
Sisodiya, SM;Free, SL;van Heyningen, V
通讯作者：
van Heyningen, V
DOI：
10.1016/s1474-4422(12)70213-2
发表时间：
2012-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Saidha S;Sotirchos ES;Ibrahim MA;Crainiceanu CM;Gelfand JM;Sepah YJ;Ratchford JN;Oh J;Seigo MA;Newsome SD;Balcer LJ;Frohman EM;Green AJ;Nguyen QD;Calabresi PA
通讯作者：
Calabresi PA
影响因子：
1.8
作者：
Jacobs, JB;Dell'Osso, LF
通讯作者：
Dell'Osso, LF
影响因子：
3.2
作者：
Moorman, AFM;Houweling, AC;Christoffels, VM
通讯作者：
Christoffels, VM
DOI：
10.1111/j.1460-9568.2008.06475.x
发表时间：
2008-10
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bayatti N;Sarma S;Shaw C;Eyre JA;Vouyiouklis DA;Lindsay S;Clowry GJ
通讯作者：
Clowry GJ