Familial Presentation of Heteroplasmic Mutation m.3291TC in the MT-TL1 Gene

Background. The rare mitochondrial DNA mutation m.3291TC was first described in a teenage boy presenting clinically with MELAS syndrome (Goto et al. 1994). Subsequently, different mitochondrial phenotypes have been associated with the heteroplasmic presence of this mutation, sometimes combining symptoms characteristic of different mitochondrial syndromes (Emmanuele et al. 2012; Liu et al. 2013) or relatively nonspecific symptoms related to energy deficiency (Uziel et al. 2000; Sunami et al. 2011; Salsano et al. 2011; de Boer et al. 2021). The pathogenicity of the variant m.3291TC has been confirmed (Yarham et al. 2013). This
study describes the clinical course of the mitochondrial disease due to the heteroplasmic variant m.3291TC in a daughter and mother within 10 years.

Case report. A teenage girl presented with WPW syndrome and slowly progressive hearing loss (HL), as well as mild myopathy in her late teens. She experienced epilepsy and stroke-like episodes (SLE) in her mid-20s with neurologic myoclonias and external ophthalmoplegia, as well as a history of depressive episodes
Her brain CT revealed several hypodensive regions in the left occipital lobe. The
patient’s mother had HL since her 20s and was diagnosed with diabetes at the age of 49. At 58 years of age, she experienced fatigue, muscular weakness and psychiatric symptoms. The brain MRI revealed vascular encephalopathy along with atrophy involving the brain and cerebellum. The
mutation m.3291TC in the MT-TL gene with different levels of heteroplasmy was identified in the mitochondrial DNA of both patients.

Discussion and conclusions. Herein, we report the familial presentation and clinical course of a rare mitochondrial DNA mutation, which has previously been described in only a few cases. It is anticipated that this report contributes to a better understanding of this extremely rare mitochondrial disorder.