A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability.
A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability.
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DOI：
10.3389/fgene.2015.00311
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发表时间：
2015
影响因子：
3.7
通讯作者：
Lenaers G
中科院分区：
文献类型：
--
作者：
Charif M;Roubertie A;Salime S;Mamouni S;Goizet C;Hamel CP;Lenaers G
导致视神经纤维损失的显性视神经病变是最常见的遗传性线粒体疾病之一。在大多数基因解决的病例中，该疾病与 OPA1 的突变有关，OPA1 编码参与网络融合、嵴结构和线粒体基因组维护的内部线粒体动力。 OPA1 裂解受两种 m-AAA 蛋白酶 SPG7 和 AFG3L2 调节，这两种蛋白酶分别参与痉挛性截瘫 7 和脊髓小脑性共济失调 28。在这里，我们在 AFG3L2 中发现了一个新的突变 c.1402C>T，修饰了一个家族中进化高度保守的精氨酸指基序中半胱氨酸中的精氨酸 468患有视神经萎缩和轻度智力障碍。眼科检查发现视盘颞侧和鼻侧视网膜神经纤维缺失，并出现红绿色色盲。因此，我们的结果表明视神经萎缩等神经眼科症状可能与 AFG3L2 突变有关，并且应提示在孤立性和综合征性遗传性视神经病患者中筛查该基因。
Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are, respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red–green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies.