Summary

Genetic counseling of families with the mitochondrial DNA variant MT-TL1 m.3243A>G may be challenging due to variable disease expressivity. In this study, we investigated the relationship between heteroplasmy levels of m.3243A>G and clinical phenotypes among 7,382  patients referred to testing due to different clinical indications.  

• Out of 7,382 samples, 50 (0.68%) carried the variant, with heteroplasmy levels ranging from 1.8% to 88%  

• Among the 50 carriers, 36 had phenotypes consistent with the variant, most commonly MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) or MIDD (maternally-inherited diabetes and deafness), with higher median heteroplasmy levels (28% overall; 32% for MELAS/MIDD)  

• Other phenotypes included isolated ophthalmologic issues, hearing loss, and cardiomyopathy  

• In contrast, patients with alternative molecular diagnoses or inconsistent phenotypes had much lower heteroplasmy levels (median 3.4%) 

The study concludes that while heteroplasmy levels and phenotypes among m.3243A>G carriers are variable, higher heteroplasmy is generally associated with classic phenotypes like MELAS and MIDD. These findings align with previous research. 

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Authors:

Rocio Sanchez Alcudia, Miko Valori, Ville Kytölä, Lotta Koskinen, Angel Aledo-Serrano, Pertteli Salmenperä, Massimiliano Gentile, Jonna Tallila, Juha Koskenvuo, Marita Isokallio