The mitochondrial tRNAAla 5587T>C and tRNALeu(CUN) 12280A>G mutations may be associated with hypertension in a Chinese family

Abstract

Hypertension is a very common cardiovascular disorder, however, the molecular mechanism underlying this disease remains poorly understood. Recently, an increasing number of studies have demonstrated that mitochondrial (mt)DNA mutations serve important roles in the pathogenesis of hypertension. The current study reported the clinical and molecular characterization of a Chinese family with maternally inherited hypertension (the penetrance of hypertension was 71.4%). In addition, the entire mitochondrial transfer (mt-t)RNA genomes was amplified using a polymerase chain reaction (PCR) and identified through direct Sanger sequencing. Additionally, the mtDNA copy number in matrilineal relatives in this family was evaluated using quantitative PCR. The sequence analysis of the 22 mt-tRNA genes led to the identification of tRNA Ala 5587T>C (thymine to cytosine) and tRNA Leu(CUN) 12280A>G (adenine to guanine) mutations. Notably, the heteroplasmic 5587T>C mutation was located at the 3' end of tRNA Ala (position 73), which is highly conserved from bacteria to human mitochondria. In addition, the 12280A>G mutation was revealed to occurs at the dihydrouridine loop of tRNA Leu(CUN) (position 15) and may decrease the steady-state level of mt-tRNA. As a result, 5587T>C and 12280A>G mutations may lead to the failure of tRNAs metabolism and subsequently cause mitochondrial protein synthesis defects. Molecular analysis revealed that patients carrying the 5587T>C and 12280A>G mutations had a lower copy number of mtDNA compared with a control with hypertension, but without the mutations, suggesting that these mutations may cause mitochondrial dysfunctions that are responsible for hypertension. Therefore, mt-tRNA Ala 5587T>C and tRNA Leu(CUN) 12280A>G mutations may be involved in the pathogenesis of hypertension in this family.

Comparative mitogenome analysis of two ectomycorrhizal fungi (Paxillus) reveals gene rearrangement, intron dynamics, and phylogeny of basidiomycetes

“…The tRNA and rRNA genes shared by the two Paxillus species also underwent base and length variations. Base variation in tRNA has been thought to affect the efficiency of amino acid transport and protein synthesis in animals (Ding et al 2019 ; Lin et al 2019 ). Further studies are needed to reveal the effect of tRNA variation on the growth and development of basidiomycete species.…”

Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation

“…Indeed, consistent with this we found that ROS production was elevated in cybrids expressing this 15910C > T mutation. Such ROS production can lead to significant damage to cellular macromolecules including DNA and proteins, potentially leading to cellular dysfunction or apoptotic cell death which, if it were to occur in cardiac muscle cells, could contribute to the observed CHD phenotype, potnetially explaining how these mutations contribute to the observed matrilineal CHD, as hypertension-associated mitochondrial tRNA Ala m.5655A > G m.5587 T > C, tRNA Leu(CUN) m.12280A > G and tRNA Met m.4467 C > A detailed previously [22][23][24].…”

Unusual Phenotype and Disease Trajectory in Kearns–Sayre Syndrome

“…ough the patient fulfilled the diagnostic criteria for KSS, he additionally presented with a plethora of manifestations, of which some have been reported earlier in KSS. In addition to the features required for diagnosing KSS, the patient presented with the known features of diabetes [4], hypocorticism (hyponatremia) [5], short stature [6], white matter lesions [7], hypoacusis [1], migraine [8], hepatopathy [9], steatosis [10], and cataract [11]. Features so far unreported in KSS include congenital anisocoria, severe caries, liver cysts, pituitary enlargement, desquamation of hands and feet, bone chondroma, aortic ectasia, dermoidal cyst, and polyposis of nasal sinuses.…”

“…Concerning the recurrent deteriorations of the phenotype during infections or spontaneously, it cannot be excluded that these conditions were in fact seizures or strokelike episodes (SLEs), which remained unrecognized and recovered spontaneously. At least 4 of these episodes were 4 Case Reports in Neurological Medicine…”

“…An argument for SLEs is that MRI at the first episode at age 36 showed subcortical T2-hyperintensities, which were also hyperintense on DWI and ADC and not confined to a vascular territory, suggesting a vasogenic edema. Whether arterial hypertension should be regarded as a manifestation of the MID is questionable but there are indications from Chinese studies that arterial hypertension can be in fact a phenotypic feature of an MID [4].…”