MELAS, MIDD and Beyond: m.3243A>G MT-TL1 Mutation in Adult Patients

Abstract

m.3243A>G MT-TL1 mutation is the most common mitochondrial DNA mutation that results in a wide spectrum of disorders in a maternally inherited pedigree. In adult patients, many present with symptoms and signs indistinguishable from acquired diseases and the correct diagnosis is often delayed after many years. Nevertheless, clues suggesting m.3243A>G usually exist early in the disease course but are only realized late. These hints, from the evolution of symptoms and signs, family background, investigation results, or a combination of these, enable the physician to make the correct diagnosis early, which is important for appropriate treatment and better patient care. As with other inheritable diseases, genetic counselling should be offered regarding the disease management, inheritance mode, recurrence risk, usefulness and limitations of genetic testing and reproductive options.

Collision-Induced Unfolding Reveals Disease-Associated Stability Shifts in Mitochondrial Transfer Ribonucleic Acids

“…61−63 Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) remain one of the most common, and often fatal, mitochondrial disorders beginning in early childhood, affecting both the nervous and muscular systems. 64 In approximately 80% of cases, an A3243G transition mutation occurring in the mt-tRNA Leu(UUR) is observed and correlated to the onset of the disorder. 65 While the current consensus is that this mutation negatively affects mitochondrial translation, the biophysical consequences of this mutation remain poorly understood.…”

“…Human mitochondria are unique in that they contain their own genome and encode for a complete set of tRNAs separate from cytosolic tRNAs . Importantly, these mt-tRNAs incur significant rates of mutation due to the highly oxidative environment native to the mitochondria, and these mutations result in several mitochondrial disorders that remain difficult to capture and characterize. − Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) remain one of the most common, and often fatal, mitochondrial disorders beginning in early childhood, affecting both the nervous and muscular systems . In approximately 80% of cases, an A3243G transition mutation occurring in the mt-tRNA Leu(UUR) is observed and correlated to the onset of the disorder .…”

Collision Induced Unfolding Reveals Disease-Associated Stability Shifts in Mitochondrial tRNAs

“…[53][54][55] Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) remain one of the most common, and often fatal, mitochondrial disorders beginning in early childhood, affecting both the nervous and muscular systems. 56 In approximately 80% of cases, an A3243G transition mutation occurring in the mt-tRNA LEU(UUR) is observed and correlated to the onset of the disorder. 57 While the current consensus is that this mutation negatively affects mitochondrial translation, the biophysical consequences of this mutation remain poorly understood.…”

Collision Induced Unfolding Reveals Disease-Associated Stability Shifts in Mitochondrial tRNAs

“…[53][54][55] Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) remain one of the most common, and often fatal, mitochondrial disorders beginning in early childhood, affecting both the nervous and muscular systems. 56 In approximately 80% of cases, an A3243G transition mutation occurring in the mt-tRNA LEU(UUR) is observed and correlated to the onset of the disorder. 57 While the current consensus is that this mutation negatively affects mitochondrial translation, the biophysical consequences of this mutation remain poorly understood.…”