Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
Cold Spring Harb Mol Case Stud. 2024 Jan 10;9(4). doi: 10.1101/mcs.a006295. Print 2023 Dec.
Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol-cytochrome reductase, are particularly rare in humans. Ubiquinol-cytochrome reductase core protein 2 () encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported -deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in : c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.
电子传递链（ETC）障碍是一组罕见的多系统疾病，由氧化磷酸化和能量产生受损引起。复合物 III（CIII）的缺乏，也称为泛醌-细胞色素 c 还原酶，在人类中特别罕见。泛醌-细胞色素 c 还原酶核心蛋白 2（）编码 CIII 的一个亚基，在二聚化中起着关键作用。已经在表现出代谢异常的患者中鉴定出几种致病性变体，包括乳酸酸中毒、高血氨症、低血糖和有机酸尿症。几乎所有先前报道的 - 缺乏患者都表现出神经发育受累，包括发育迟缓和结构性脑异常。在这里，我们描述了一个女孩，她在 3 岁时出现乳酸酸中毒、高血氨症和低血糖，但到 15 岁时没有任何神经发育功能障碍的证据。全外显子组测序显示两个新变体的复合杂合性：c.1189G>A；p.Gly397Arg 和 c.437T>C；p.Phe146Ser。在这里，我们讨论了患者的临床表现和这两个错义变体的可能致病性。
