Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease.
Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease.
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DOI：
10.1016/j.ymgme.2022.09.002
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发表时间：
2022-11
影响因子：
3.8
通讯作者：
Ehinger, Johannes K.
中科院分区：
文献类型：
--
作者：
Elander, Johanna;McCormick, Elizabeth M.;Varendh, Maria;Stenfeldt, Karin;Ganetzky, Rebecca D.;Goldstein, Amy;Zolkipli-Cunningham, Zarazuela;MacMullen, Laura E.;Xiao, Rui;Falk, Marni J.;Ehinger, Johannes K.
关键词：
在费城儿童医院线粒体医学前沿项目的193例原发性线粒体疾病（PMD）连续受试者的回顾性队列研究中，我们评估了不同遗传病因PMD的感音神经性听力损失（SNHL）的患病率、严重程度和发病时间。受试者按遗传学诊断分组：线粒体DNA（mtDNA）致病变异、单个大规模mtDNA缺失（SLSMD）或核DNA（nDNA）致病变异。SNHL在27%的PMD受试者中得到听力测定证实（20%为mtDNA致病性变异，58%为SLSMD，25%为nDNA致病性变异）。SLSMD对SNHL的优势比最高。79%的病例SNHL发生在舌后，有趣的是，在所有mtDNA致病变异和SLSMD的病例中，由于nDNA变异，SNHL与PMD显著不同。发病以学龄期为主。定期的听力学评估对PMD患者很重要，mtDNA病因的PMD应被认为是儿童患者和年轻成人舌后SNHL发作的鉴别诊断，特别是在多系统临床受累的情况下。致病性mtDNA变异和SLSMD是先天性听力损失受试者中不太可能的病因。
In this retrospective cohort study of 193 consecutive subjects with primary mitochondrial disease (PMD) seen at the Children’s Hospital of Philadelphia Mitochondrial Medicine Frontier Program, we assessed prevalence, severity, and time of onset of sensorineural hearing loss (SNHL) for PMD of different genetic etiology. Subjects were grouped by genetic diagnosis: mitochondrial DNA (mtDNA) pathogenic variants, single large-scale mtDNA deletions (SLSMD), or nuclear DNA (nDNA) pathogenic variants. SNHL was audiometrically confirmed in 27% of PMD subjects (20% in mtDNA pathogenic variants, 58% in SLSMD and 25% in nDNA pathogenic variants). SLSMD had the highest odds ratio for SNHL. SNHL onset was post-lingual in 79% of cases, and interestingly in all cases with mtDNA pathogenic variants and SLSMD, significantly different from PMD due to nDNA variants. Onset during school age dominated. Regular audiologic assessment is important for PMD patients, and PMD of mtDNA etiology should be considered as a differential diagnosis in pediatric patients and young adults with post-lingual SNHL onset, particularly in the setting of multi-system clinical involvement. Pathogenic mtDNA variants and SLSMD are less likely etiologies in subjects with congenital hearing loss.
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影响因子：
12.3
作者：
Santarelli R
通讯作者：
Santarelli R
与成年线粒体疾病有关的核和线粒体DNA突变的患病率。
影响因子：
11.2
作者：
Gorman GS;Schaefer AM;Ng Y;Gomez N;Blakely EL;Alston CL;Feeney C;Horvath R;Yu-Wai-Man P;Chinnery PF;Taylor RW;Turnbull DM;McFarland R
通讯作者：
McFarland R
影响因子：
3.6
作者：
Barcelos I;Shadiack E;Ganetzky RD;Falk MJ
通讯作者：
Falk MJ
影响因子：
5.2
作者：
Downie, Lilian;Halliday, Jane;Amor, David J.
通讯作者：
Amor, David J.
影响因子：
2
作者：
Mehta, Devanshi;Noon, Sarah E.;Krantz, Ian D.
通讯作者：
Krantz, Ian D.