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

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.
Source: BBA Clinical - Category: Biochemistry Source Type: research