Department of Pediatrics, Inner Mongolia Maternal and Child Health Hospital, Hohhot, People's Republic of China.
Neuropediatrics. 2024 Jun;55(3):178-182. doi: 10.1055/a-1949-9310. Epub 2022 Sep 23.
The aim of the study is to explore the clinical and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous pathogenic variants, and to improve clinicians' awareness of the disease.
The proband was a girl of first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay, intellectual disability, developmental retardation after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. The clinical performance, diagnosis, treatment process, and gene characteristics of COXPD21 caused by TARS2 of the case were analyzed, reviewed, and compared with the literature from the CNKI, Wanfang Data, and biomedical literature database (PubMed) until November 2021.
The child was diagnosed with COXPD21 after two heterozygous variants in the TARS2 gene were found via whole exome sequencing. One of the variants was c.1679(exon14) A > C (p.Asp560Ala) missense, derived from the mother, and the other was c.1036(exon10)C > T (p.Arg346Cys) missense, derived from the father. The literature was searched and reviewed with the keywords "mitochondrial encephalomyopathy," "TARS2," and "combination oxidative phosphorylation deficiency type 21." A total of four complete domestic and foreign cases were collected from the literature search.
COXPD21 onset by a complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported in China and abroad.
本研究旨在探讨 TARS2 复合杂合致病性变异引起的联合氧化磷酸化缺陷 21 型（COXPD21）的临床和遗传特征，提高临床医生对该病的认识。
先证者为初产妇女孩，临床表现为反复难治性低钾血症、听力障碍、发育迟缓、智力障碍、感染后发育迟缓、四肢肌肉张力增高、血清乳酸增高等。分析、回顾并比较了该病例 TARS2 所致 COXPD21 的临床表型、诊断、治疗过程及基因特征，并与中国知网（CNKI）、万方数据、生物医学文献数据库（PubMed）截至 2021 年 11 月的文献进行了对比。
经全外显子测序发现 TARS2 基因存在 2 个杂合变异，患儿被诊断为 COXPD21。其中一个变异为 c.1679(exon14)A>G(p.Asp560Ala)错义，来自母亲；另一个变异为 c.1036(exon10)C>T(p.Arg346Cys)错义，来自父亲。检索并以“线粒体脑肌病”“TARS2”和“联合氧化磷酸化缺陷 21 型”为关键词查阅文献，共收集到国内外完全病例 4 例。
TARS2 复合杂合变异引起的 COXPD21 发病罕见，中国和国外报道较少。
