Leigh syndrome: Clinical features and biochemical and DNA abnormalities

Annals of Neurology - Tập 39 Số 3 - Trang 343-351 - 1996
S. Rahman1, Rozanne B. Blok2, H H Dahl2, D. M. Danks2, Denise M. Kirby2, C.W. Chow3, John Christodoulou4, David R. Thorburn2
1Murdoch Institute, Royal Children's Hospital, Parkville, Victoria, Australia
2The Murdoch Institute for Research into Birth Defects, Royal Children Hospital, Melbourne, Australia
3Department of Anatomical Pathology, Royal Children's Hospital, Melbourne, Australia
4Department of Paediatrics and Child Health, Children's Hospital, Sydney, Australia

Tóm tắt

AbstractWe 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 Elα 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 (1 1 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.

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Annals of Neurology

Tập 39 Số 3

343-351

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