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Three families with 'de novo' m.3243A > G mutation

Lookup NU author(s): Dr Charlotte Alston, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2016 . The m.3243A > G mutation is the most prevalent, disease-causing mitochondrial DNA (mtDNA) mutation. In a national cohort study of 48 families harbouring the m.3243A > G mutation, we identified three families in which the mutation appeared to occur sporadically within these families. In this report we describe these three families. Based on detailed mtDNA analysis of three different tissues using two different quantitative pyrosequencing assays with sensitivity to a level of 1% mutated mtDNA, we conclude that the m.3243A > G mutation has arisen de novo in each of these families. The symptomatic carriers presented with a variety of symptoms frequently observed in patients harbouring the m.3243A > G mutation. A more severe phenotype is seen in the de novo families compared to recent cohort studies, which might be due to reporting bias.The observation that de novo m.3243A > G mutations exist is of relevance for both diagnostic investigations and genetic counselling. Firstly, even where there is no significant (maternal) family history in patients with stroke-like episodes, diabetes and deafness or other unexplained organ dysfunction, the m.3243A > G mutation should be screened as a possible cause of the disease. Second, analysis of maternally-related family members is highly recommended to provide reliable counselling for these families, given that the m.3243A > G mutation may have arisen de novo.

Publication metadata

Author(s): de Laat P, Janssen MCH, Alston CL, Taylor RW, Rodenburg RJT, Smeitink JAM

Publication type: Article

Publication status: Published

Journal: BBA Clinical

Year: 2016

Volume: 6

Pages: 19-24

Print publication date: 01/12/2016

Online publication date: 29/04/2016

Acceptance date: 28/04/2016

Date deposited: 05/04/2017

ISSN (print): 2214-6474

Publisher: Elsevier


DOI: 10.1016/j.bbacli.2016.04.007


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