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Sequence variation in mitochondrial complex I genes: Mutation or polymorphism?

Lookup NU author(s): Dr Anna MitchellORCiD, Dr Joanna Elson, Professor Robert Taylor, Emeritus Professor Doug Turnbull


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Background: Defects of the mitochondrial genome are recognised as common causes of genetic disease. Sequencing of large portions or even the entire mitochondrial genome is routine in many laboratories for the investigation of mitochondrial disease. However, establishing whether a detected sequence change is polymorphic or pathogenic is still a major difficulty because of its highly polymorphic nature. This has major implications for the patient and the family. Objective: To describe a scoring system for determining the likelihood that a given sequence variant in one of the seven mitochondrially encoded complex I (MTND) genes is truly pathogenic. Results: The scoring system was applied to 50 reported MTND mutations. Using this system, 21 of the mutations analysed fell into the group of neutral sequence variants, 10 were classified as possibly pathogenic, three as probably pathogenic, and 16 as almost certainly pathogenic. Conclusions: The proposed scoring system should advance the interpretation of sequence variants and ensure that candidate pathogenic mutations are rigorously investigated.

Publication metadata

Author(s): Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM

Publication type: Article

Publication status: Published

Journal: Journal of Medical Genetics

Year: 2006

Volume: 43

Issue: 2

Pages: 175-179

ISSN (print): 0022-2593

ISSN (electronic): 1468-6244

Publisher: BMJ Group


DOI: 10.1136/jmg.2005.032474

PubMed id: 15972314


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Funder referenceFunder name
Wellcome Trust
074454Wellcome Trust