Department of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, P.R. China.
Department of Medical Genetics, Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, China.
Orphanet J Rare Dis. 2024 Oct 11;19(1):376. doi: 10.1186/s13023-024-03365-w.
Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21.
TARS2 中的双等位致病性变异导致 21 型联合氧化磷酸化缺陷（COXPD21，MIM#615918），这是一种罕见的线粒体脑肌病（ME），其特征为早发性严重轴性张力减退、四肢张力亢进、精神运动发育迟缓、癫痫和脑异常。迄今为止，已鉴定出大约 28 名 COXPD21 患者和 28 种 TARS2 变异体。在这项研究中，我们报告了来自三个无关联的中国家庭的另外四名由 TARS2 中的致病性变异引起的线粒体脑肌病患者，并描述了新的临床表型和基因型信息。除了两个新的变异（c.512G > A，p.Arg171Lys；c.988dup，p.Arg330Lysfs*4）外，在 6 名 COXPD21 患者中发现了一个先前报道的变异（c.470C > G，p.Thr157Arg）再次出现，但在其他种族的人群中不存在。我们的发现扩展了 TARS2 的突变谱，并证实 c.470C > G 是一种中国特有的起始突变。在我们的患者中观察到的新表型，包括胎儿运动减少、眼部异常和睡眠不规则，丰富了 COXPD21 的临床特征。
