A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality
A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality
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DOI：
10.1203/01.pdr.0000117844.73436.68
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发表时间：
2004-05-01
影响因子：
3.6
通讯作者：
Comi, GP
中科院分区：
文献类型：
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作者：
Crimi, M;Papadimitriou, A;Comi, GP
我们描述了一个新的线粒体DNA突变的男婴，他表现出Leigh综合征的临床和磁共振成像特征，并在9个月时死亡。据报道，患者在出生后的头几个月发育正常。在5个月的时候，他表现出严重的全身性低眼压、眼球震颤和缺乏眼神接触。实验室检查显示血清和脑脊液中乳酸和丙酮酸均升高。脑磁共振成像显示基底节、脑干和丘脑有多处坏死性病变。肌肉组织病理学检查不明显，而呼吸链酶分析显示严重的复合体I缺乏。患者在9岁时死于酸中毒昏迷。对整个mtDNA的序列分析发现了一个新的T10158C突变，具有不同的组织异质性(肌肉：83%；血液：48%)。在他未受感染的母亲的血液中没有检测到这种突变。在NADH脱氢酶亚单位3(ND3)的一个高度保守的区域，这种转变将丝氨酸残基转变为脯氨酸。这是首次在早期致死的Leigh综合征中描述线粒体ND3基因。
We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality.