PDF(Pubmed)
Abstract：
UNASSIGNED: This study aimed to examine the frequencies of mt-tRNAGlu variants in 180 pediatric patients with non-syndromic hearing loss (NSHL) and 100 controls.
UNASSIGNED: Sanger sequencing was performed to screen for mt-tRNAGlu variants. These mitochondrial DNA (mtDNA) pathogenic mutations were further assessed using phylogenetic conservation and haplogroup analyses. We also traced the origins of the family history of probands carrying potential pathogenic mtDNA mutations. Mitochondrial functions including mtDNA content, ATP and reactive oxygen species (ROS) were examined in cells derived from patients carrying the mt-tRNAGlu A14692G and CO1/tRNASer(UCN) G7444A variants and controls.
UNASSIGNED: We identified four possible pathogenic variants: m.T14709C, m.A14683G, m.A14692G and m.A14693G, which were found in NSHL patients but not in controls. Genetic counseling suggested that one child with the m.A14692G variant had a family history of NSHL. Sequence analysis of mtDNA suggested the presence of the CO1/tRNASer(UCN) G7444A and mt-tRNAGlu A14692G variants. Molecular analysis suggested that, compared with the controls, patients with these variants exhibited much lower mtDNA copy numbers, ATP production, whereas ROS levels increased (p<0.05 for all), suggesting that the m.A14692G and m.G7444A variants led to mitochondrial dysfunction.
UNASSIGNED: mt-tRNAGlu variants are important risk factors for NSHL.
The main aim of our study was to explore the association between the mt-tRNAGlu variants and hearing loss. We found that m.T14709C, m.A14683G, m.A14692G and m.A14693G variants were associated with hearing impairments, these variants localized at extremely conserved nucleotides of mt-tRNAGlu and may result a failure in tRNA metabolism, furthermore, patients with mt-tRNAGlu variants exhibited much lower levels of mtDNA copy number, ATP as compared with controls, whereas ROS increased. As a result, mt-tRNAGlu variants may serve as biomarkers for mitochondrial deafness, and screening for tRNAGlu variants is recommended for early detection and diagnosis of mitochondrial deafness.
UNASSIGNED: Sanger sequencing was performed to screen for mt-tRNAGlu variants. These mitochondrial DNA (mtDNA) pathogenic mutations were further assessed using phylogenetic conservation and haplogroup analyses. We also traced the origins of the family history of probands carrying potential pathogenic mtDNA mutations. Mitochondrial functions including mtDNA content, ATP and reactive oxygen species (ROS) were examined in cells derived from patients carrying the mt-tRNAGlu A14692G and CO1/tRNASer(UCN) G7444A variants and controls.
UNASSIGNED: We identified four possible pathogenic variants: m.T14709C, m.A14683G, m.A14692G and m.A14693G, which were found in NSHL patients but not in controls. Genetic counseling suggested that one child with the m.A14692G variant had a family history of NSHL. Sequence analysis of mtDNA suggested the presence of the CO1/tRNASer(UCN) G7444A and mt-tRNAGlu A14692G variants. Molecular analysis suggested that, compared with the controls, patients with these variants exhibited much lower mtDNA copy numbers, ATP production, whereas ROS levels increased (p<0.05 for all), suggesting that the m.A14692G and m.G7444A variants led to mitochondrial dysfunction.
UNASSIGNED: mt-tRNAGlu variants are important risk factors for NSHL.
The main aim of our study was to explore the association between the mt-tRNAGlu variants and hearing loss. We found that m.T14709C, m.A14683G, m.A14692G and m.A14693G variants were associated with hearing impairments, these variants localized at extremely conserved nucleotides of mt-tRNAGlu and may result a failure in tRNA metabolism, furthermore, patients with mt-tRNAGlu variants exhibited much lower levels of mtDNA copy number, ATP as compared with controls, whereas ROS increased. As a result, mt-tRNAGlu variants may serve as biomarkers for mitochondrial deafness, and screening for tRNAGlu variants is recommended for early detection and diagnosis of mitochondrial deafness.
摘要：
■本研究旨在检查180例非综合征性听力损失（NSHL）儿科患者和100例对照中mt-tRNAGlu变异的频率。
■进行Sanger测序以筛选mt-tRNAGlu变体。使用系统发育保守和单倍群分析进一步评估了这些线粒体DNA（mtDNA）致病性突变。我们还追踪了携带潜在致病性mtDNA突变的先证者家族史的起源。线粒体功能，包括mtDNA含量，在来自携带mt-tRNAGluA14692G和CO1/tRNASer（UCN）G7444A变体和对照的患者的细胞中检查了ATP和活性氧（ROS）。
■我们确定了四种可能的致病变体：m.T14709C，m.A14683G,m.A14692G和m.A14693G，在NSHL患者中发现，但未在对照组中发现。遗传咨询表明，一个患有m.A14692G变体的孩子有NSHL家族史。mtDNA的序列分析表明存在CO1/tRNASer(UCN)G7444A和mt-tRNAGluA14692G变体。分子分析表明,与对照组相比，这些变异的患者表现出更低的mtDNA拷贝数，ATP生产，而ROS水平增加(全部p<0.05)，表明m.A14692G和m.G7444A变体导致线粒体功能障碍。
■mt-tRNAGlu变异体是NSHL的重要危险因素。
我们研究的主要目的是探索mt-tRNAGlu变异与听力损失之间的关联。我们发现m.T14709C,m.A14683G,m.A14692G和m.A14693G变体与听力障碍有关，这些变体位于mt-tRNAGlu的极其保守的核苷酸处，可能导致tRNA代谢失败，此外，患有mt-tRNAGlu变异的患者表现出更低水平的mtDNA拷贝数，ATP与对照组相比，而ROS增加。因此,mt-tRNAGlu变体可以作为线粒体耳聋的生物标志物，建议筛查tRNAGlu变异体以早期发现和诊断线粒体耳聋。
■进行Sanger测序以筛选mt-tRNAGlu变体。使用系统发育保守和单倍群分析进一步评估了这些线粒体DNA（mtDNA）致病性突变。我们还追踪了携带潜在致病性mtDNA突变的先证者家族史的起源。线粒体功能，包括mtDNA含量，在来自携带mt-tRNAGluA14692G和CO1/tRNASer（UCN）G7444A变体和对照的患者的细胞中检查了ATP和活性氧（ROS）。
■我们确定了四种可能的致病变体：m.T14709C，m.A14683G,m.A14692G和m.A14693G，在NSHL患者中发现，但未在对照组中发现。遗传咨询表明，一个患有m.A14692G变体的孩子有NSHL家族史。mtDNA的序列分析表明存在CO1/tRNASer(UCN)G7444A和mt-tRNAGluA14692G变体。分子分析表明,与对照组相比，这些变异的患者表现出更低的mtDNA拷贝数，ATP生产，而ROS水平增加(全部p<0.05)，表明m.A14692G和m.G7444A变体导致线粒体功能障碍。
■mt-tRNAGlu变异体是NSHL的重要危险因素。
我们研究的主要目的是探索mt-tRNAGlu变异与听力损失之间的关联。我们发现m.T14709C,m.A14683G,m.A14692G和m.A14693G变体与听力障碍有关，这些变体位于mt-tRNAGlu的极其保守的核苷酸处，可能导致tRNA代谢失败，此外，患有mt-tRNAGlu变异的患者表现出更低水平的mtDNA拷贝数，ATP与对照组相比，而ROS增加。因此,mt-tRNAGlu变体可以作为线粒体耳聋的生物标志物，建议筛查tRNAGlu变异体以早期发现和诊断线粒体耳聋。
