Alstrup Morten, Vogel Ida, Sandager Puk, Blechingberg Jenny, Becher Naja, Østergaard Elsebet
Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark.
Center for Fetal Diagnostics, Department of Clinical Medicine Aarhus University Hospital Aarhus Denmark.
JIMD Rep. 2021 Mar 5;59(1):20-25. doi: 10.1002/jmd2.12209. eCollection 2021 May.
The C1QBP protein (complement component 1 Q subcomponent-binding protein), encoded by the C1QBP gene, is a multifunctional protein predominantly localized in the mitochondrial matrix. Biallelic variants have previously been shown to give rise to combined respiratory-chain deficiencies with variable phenotypic presentation, severity, and age at onset, from intrauterine with a mostly lethal course, to a late-onset mild myopathy. We present two fetuses, one male and one female, of first-cousin parents, with severe intrauterine growth retardation, oligo/anhydramnios, edema, and cardiomyopathy as the most prominent prenatal symptoms. Both fetuses showed no copy number variants by chromosome microarray analysis. Analysis of a fibroblast culture from one of the fetuses showed deficiency of respiratory chain complex IV, and using exome sequencing, we identified homozygosity for a novel variant in in both fetuses. To our knowledge, only six patients with pathogenic variants in have been reported previously and with this report, we add a novel pathogenic variant in found in two related fetuses.
由C1QBP基因编码的C1QBP蛋白（补体成分1 Q亚成分结合蛋白）是一种主要定位于线粒体基质的多功能蛋白。此前已表明，双等位基因变异会导致呼吸链联合缺陷，其表型表现、严重程度和发病年龄各不相同，从宫内发病且大多致命，到迟发性轻度肌病。我们报告了一对表亲父母的两个胎儿，一男一女，他们有严重的宫内生长迟缓、羊水过少/无羊水、水肿和心肌病等最突出的产前症状。通过染色体微阵列分析，两个胎儿均未显示拷贝数变异。对其中一个胎儿的成纤维细胞培养物进行分析，结果显示呼吸链复合物IV缺乏，通过外显子组测序，我们在两个胎儿中均发现了一个新变异的纯合性。据我们所知，此前仅报道过6例携带该基因致病变异的患者，通过本报告，我们在两个相关胎儿中发现了一个新的致病变异。
