Zhai Yujia, Chen Jing, Yang Shuo, Wang He, Xiao Yuanyuan, Liu Shanling
Department of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Front Genet. 2025 Apr 25;16:1539288. doi: 10.3389/fgene.2025.1539288. eCollection 2025.
F-box and leucine-rich repeat protein 4 (FBXL4) plays a crucial role in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. The variations in the gene can give rise to encephalomyopathy mitochondrial DNA depletion syndrome-13 (MTDPS13) characterized by the reduction of mtDNA copy number, leading to deficiencies in mitochondrial functions, which is a serious and rare autosomal recessive genetic disorder. Patients with variations are usually diagnosed due to the emergence of symptoms in the early stages of life. Commonly observed are lactic acidemia, developmental retardation, and hypotonia. A portion of patients may be accompanied by comorbidities such as cardiovascular diseases, epilepsy, ophthalmopathy, hearing impairment, and movement disorders. Currently, there have been no reported cases of prenatal diagnosis for gene variations. Here, we report for the first time the prenatal diagnosis of a fetus with a compound heterozygous mutation in the gene (NM_012160.5: c.1288C>T, p. Arg430* and c.518_523del, p. Glu173_Leu175delinsVal) by trio-WES, the nonsense mutation (c.1288C>T) was reported only once in an unrelated individual and no detailed clinical phenotype; the deletion mutation (c.518_523del) has not been reported yet. Additionally, we monitor prenatal phenotypes of fetus at different stages of pregnancy using ultrasound and magnetic resonance imaging (MRI), present prenatally with nuchal translucency (NT) thickening and progressive brain developmental abnormalities. Our report indicates that the application of trio whole exome sequencing (trio-WES) and imaging monitoring can facilitate prenatal diagnosis of gene-related MTDPS13, and this will modify the decision-making process for couples with variations.
F-box和富含亮氨酸重复序列蛋白4（FBXL4）在线粒体生物能量学、线粒体DNA（mtDNA）维持以及线粒体动力学中发挥着关键作用。该基因的变异可引发线粒体脑肌病伴线粒体DNA耗竭综合征13型（MTDPS13），其特征为mtDNA拷贝数减少，导致线粒体功能缺陷，这是一种严重且罕见的常染色体隐性遗传疾病。携带变异的患者通常在生命早期出现症状时被诊断出来。常见的症状有乳酸性血症、发育迟缓以及肌张力减退。部分患者可能伴有心血管疾病、癫痫、眼病、听力障碍和运动障碍等合并症。目前，尚无该基因变异的产前诊断报告。在此，我们首次报告通过三联体全外显子测序（trio-WES）对一名胎儿进行产前诊断，该胎儿的该基因存在复合杂合突变（NM_012160.5: c.1288C>T，p.Arg430*和c.518_523del，p.Glu173_Leu175delinsVal），其中无义突变（c.1288C>T）仅在一名无关个体中被报道过一次，且无详细的临床表型；缺失突变（c.518_523del）尚未见报道。此外，我们使用超声和磁共振成像（MRI）监测孕期不同阶段胎儿的产前表型，该胎儿产前表现为颈部透明带（NT）增厚和进行性脑发育异常。我们的报告表明，三联体全外显子测序（trio-WES）和影像监测的应用有助于对与该基因相关的MTDPS13进行产前诊断，这将改变携带该变异夫妇的决策过程。
