Leigh syndrome: Clinical features and biochemical and DNA abnormalities
Leigh syndrome: Clinical features and biochemical and DNA abnormalities
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DOI：
10.1002/ana.410390311
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发表时间：
1996-03-01
影响因子：
11.2
通讯作者：
Thorburn, DR
中科院分区：
文献类型：
--
作者：
Rahman, S;Blok, RB;Thorburn, DR
我们调查了来自56个家系的67例澳大利亚病例的Leigh综合征的病因，其中35例确诊，32例具有一些非典型特征。在两组中均测定了生化或DNA缺陷，即严格定义组为80%，“Leigh样”组为41%。11例患者有线粒体DNA点突变（核苷酸[nt] 8993 T至G，nt 8993 T至C，或nt 8344 A至G），1例Leigh样患者有异质性缺失。29例患者有酶缺陷，即13例呼吸链复合物I，9例复合物IV和7例丙酮酸脱氢酶复合物（PDHC）。复合物I缺乏症比以前认识到的更常见。6名PDHC缺陷患者在编码PDHC E1 α亚基的X染色体基因中发生突变。父母的血缘关系表明，常染色体隐性遗传在两个复杂的IV缺陷的同胞。我们发现临床特征和基本缺陷之间没有很强的相关性。常染色体隐性遗传的假设（过去常被认为是隐性遗传）在发现病因的患者中有近一半（28例严格定义的患者中有11例，41例患者中有18例）是错误的，如果要提供可靠的遗传咨询，必须确定特定的缺陷。
We investigated the etiology of Leigh syndrome in 67 Australian cases from 56 pedigrees, 35 with a firm diagnosis and 32 with some atypical features. Biochemical or DNA defects were determined in both groups, ie, 80% in the tightly defined group and 41% in the ''Leigh-like'' group. Eleven patients had mitochondrial DNA point mutations (nucleotide [nt] 8993 T to G, nt 8993 T to C, or nt 8344 A to G) and 1 Leigh-like patient had a heteroplasmic deletion. Twenty-nine patients had enzyme defects, ie, 13 respiratory chain complex I, 9 complex IV, and 7 pyruvate dehydrogenase complex (PDHC). Complex I deficiency is more common than recognized previously. Six PDHC-deficient patients had mutations in the X-chromosomal gene encoding the E1 alpha subunit of PDHC. Parental consanguinity suggested autosomal recessive inheritance in two complex IV-deficient sibships. We found no strong correlation between the clinical features and basic defects. An assumption of autosomal recessive inheritance (frequently made in the past) would have been wrong in nearly one-half (11 of 28 tightly defined and 18 of 41 total patients) of those in whom a cause was found. A specific defect must be identified if reliable genetic counseling is to be provided.