Novel pathogenic UQCRC2 variants in a female with normal neurodevelopment.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI:10.1101/mcs.a006295

Lea Abou Haidar, Robert C Harris, Panayotis Pachnis, Hongli Chen, Garrett K Gotway, Min Ni, Ralph J DeBerardinis

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Abstract

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 c reductase, are particularly rare in humans. Ubiquinol-cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-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 UQCRC2: 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.

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一名神经发育正常的女性的新型致病性UQCRC2变体。

电子传输链（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），也称为泛醌醇细胞色素c还原酶，在人类中特别罕见。泛素细胞色素c还原酶核心蛋白2（UQCRC2）编码在二聚化中起关键作用的CIII亚基。在出现代谢异常的患者中发现了几种致病性UQCRC2变体，包括乳酸酸中毒、高氨血症、低血糖和器质性酸尿。几乎所有先前报道的UQCRC2缺陷患者都表现出神经发育障碍，包括发育迟缓和大脑结构异常。在这里，我们描述了一名女孩，她在3岁时出现乳酸酸中毒、高氨血症和低血糖，但在15岁时没有表现出任何神经发育功能障碍的证据。全外显子组测序显示UQCRC2中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种错义变体的可能致病性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

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0.00%

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期刊介绍： Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.