Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL.
Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL.
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DOI：
10.3390/genes11111325
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发表时间：
2020-11-09
期刊：
影响因子：
3.5
通讯作者：
Okazaki Y
中科院分区：
文献类型：
--
作者：
Borna NN;Kishita Y;Sakai N;Hamada Y;Kamagata K;Kohda M;Ohtake A;Murayama K;Okazaki Y
Leigh综合征(LS)最常见的特征是局灶性、双侧和对称性脑损害，白质脑病累及脑干和脊髓，乳酸升高(LBSL)是一种罕见的疾病，其特征是进行性锥体、小脑和背柱功能障碍。我们描述了一例婴儿起病的神经变性、精神运动迟缓、易怒、低眼压和眼球震颤。脑MRI显示大脑深部白质、皮质脊髓背柱束和锥体的信号异常，类似于重症LBSL的MRI模式，并累及基底节和丘脑，类似LS的放射学特征。我们通过外显子测序鉴定了NDUFV1(NADH：泛醌氧化还原酶核心亚单位V1)的双等位基因功能丧失突变，其中一个是新的(c.756delC，p.253Glnfs*44)，另一个是已报道的(c.1156C>；T，p.Arg386Cys)。生化和功能分析显示乳酸酸中毒，复合体I(CI)组装和酶缺乏，NDUFV1蛋白丢失。互补分析恢复NDUFV1蛋白、CI组装和CI酶水平。该病例的临床和放射学特征符合与NDUFV1突变相关的LS和LBSL的表型。
Leigh syndrome (LS) is most frequently characterized by the presence of focal, bilateral, and symmetric brain lesions Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare condition, characterized by progressive pyramidal, cerebellar, and dorsal column dysfunction. We describe a case with infantile-onset neurodegeneration, psychomotor retardation, irritability, hypotonia, and nystagmus. Brain MRI demonstrated signal abnormalities in the deep cerebral white matter, corticospinal and dorsal column tracts, and pyramids, which resemble the MRI pattern of a severe form of LBSL, and involvement of basal ganglia and thalamus that resemble the radiological features of LS. We identified biallelic loss-of-function mutations, one novel (c.756delC, p.Thr253Glnfs*44) and another reported (c.1156C > T, p.Arg386Cys), in NDUFV1 (NADH:Ubiquinone Oxidoreductase Core Subunit V1) by exome sequencing. Biochemical and functional analyses revealed lactic acidosis, complex I (CI) assembly and enzyme deficiency, and a loss of NDUFV1 protein. Complementation assays restored the NDUFV1 protein, CI assembly, and CI enzyme levels. The clinical and radiological features of this case are compatible with the phenotype of LS and LBSL associated with NDUFV1 mutations.
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