Phenotype-genotype correlations in Leigh syndrome : new insights from a multicentre study of 96 patients

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Sofou , K , de Coo , I F M , Ostergaard , E , Isohanni , P , Naess , K , De Meirleir , L , Tzoulis , C , Uusimaa , J , Lönnqvist , T , Bindoff , L A , Tulinius , M & Darin , N 2018 , ' Phenotype-genotype correlations in Leigh syndrome : new insights from a multicentre study of 96 patients ' , Journal of Medical Genetics , vol. 55 , no. 1 , pp. 21-27 .

Title: Phenotype-genotype correlations in Leigh syndrome : new insights from a multicentre study of 96 patients
Author: Sofou, Kalliopi; de Coo, Irenaeus F. M.; Ostergaard, Elsebet; Isohanni, Pirjo; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; Lönnqvist, Tuula; Bindoff, Laurence Albert; Tulinius, Mar; Darin, Niklas
Contributor organization: Research Programme for Molecular Neurology
Research Programs Unit
Anu Wartiovaara / Principal Investigator
Children's Hospital
University of Helsinki
Lastenneurologian yksikkö
HUS Children and Adolescents
Date: 2018-01
Language: eng
Number of pages: 7
Belongs to series: Journal of Medical Genetics
ISSN: 0022-2593
Abstract: Background Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored. Objective We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients. Methods We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases. Results We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m. 8993T> G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m. 8993T> C mutation. Conclusion Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.
3112 Neurosciences
3123 Gynaecology and paediatrics
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: acceptedVersion

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