Background: Multiple acyl-coenzyme A (CoA) dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from mutations in the ETFDH gene. It is characterized by a wide spectrum of clinical symptoms, of which polycystic kidney disease is a specific phenotype of early-onset MADD. This study aims to broaden the genetic mutation spectrum of ETFDH gene. And we clarify the pathogenic mechanism of polycystic kidney caused by the loss of function of the ETFDH gene through in vitro experiments. Results: Compound heterozygous variants in ETFDH (NM_004453: c.487 + 2 T > A, c.1395 T > G and c.1773–1774 del AT(in cis with c.1395 T > G) were identifed via trio-Whole Exome Sequencing (trio-WES) and confirmed pathogenic through Minigene Splice Assay and RT-PCR. This study, for the first time, demonstrated through both in vivo and in vitro experiments that c.487 + 2 T > A mutation lead to mRNA degradation through nonsense-mediated decay (NMD). Further cell experiments showed that downregulation of ETFDH gene led to lipid accumulation, enhanced oxidative stress, and upregulation of ZNF267 expression. Conclusions: This study clarify the pathogenicity of c.487 + 2 T > A and c.1395 T > G mutations, aiding in the diagnosis and genetic counseling of ETFDH in clinical practice. The significance of this study is to reveal that ETFDH gene may be a key regulatory gene in the development of polycystic kidney.

Dietary fat and fatty acid intakes impact the occurrence and development of several cancers. However, the evidence regarding fat and fatty acid intake and ovarian cancer (OC) survival is limited. The Ovarian Cancer Follow-Up Study (OOPS), a prospective cohort study, analyzed data collected from 703 OC patients. Deaths were ascertained via medical records and active follow-up. Dietary intake was derived from a validated food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for association evaluation. Furthermore, several subgroup and sensitivity analyses were also performed. A total of 130 patients died during a median follow-up of 37.17 (interquartile: 24.73–50.17) months. Relative to the lowest tertile of intake, patients with the highest tertile of total fat (HR = 1.87, 95% CI = 1.01–3.49), total fatty acid (HR = 2.20, 95% CI = 1.27–3.80), total saturated fatty acid (SFA) (HR = 2.02, 95% CI = 1.22–3.34), shorter-chain SFA (HR = 1.59, 95% CI = 1.03–2.47), long-chain SFA (HR = 1.69, 95% CI = 1.03–2.77), total monounsaturated fatty acid (MUFA) (HR = 1.77, 95% CI = 1.02–3.05), and animal-based MUFA (HR = 2.05, 95% CI = 1.17–3.58) intake had higher all-cause mortality risk. In contrast, individuals in the highest tertile of egg fat (HR = 0.57, 95% CI = 0.35–0.92) and fruit and vegetable fat (HR = 0.48, 95% CI = 0.31–0.75) intake exhibited a reduced risk of all-cause mortality. Additionally, significant positive associations with all-cause mortality were identified for the consumption of several common fatty acids, including capric acid (HR = 1.92, 95% CI = 1.23–3.00), myristic acid (HR = 1.86, 95% CI = 1.15–3.02), palmitic acid (HR = 1.72, 95% CI = 1.07–2.76), stearic acid (HR = 1.93, 95% CI = 1.12–3.31), and oleic acid (HR = 1.96, 95% CI = 1.13–3.40), when comparing the highest to the lowest tertile of intake. We identified a linkage of higher intake of total fats, total fatty acids, SFAs, shorter-chain SFAs, long-chain SFAs, total MUFAs, and animal-based MUFAs with increased all-cause mortality of OC patients. Conversely, consumption of egg fats and fruit and vegetable fats demonstrated inverse associations with all-cause mortality.