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Objective: To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed. Methods: Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen‐2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords. Results: The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole‐exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions. Conclusion: MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole‐exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN), which is the main cause of renal failure in end-stage renal disease, is becoming a common chronic renal disease worldwide. Mendelian randomization (MR) is a genetic tool that is widely used to minimize confounding and reverse causation when identifying the causal effects of complex traits. In this study, we conducted an integrated multiple microarray analysis and large-scale plasma proteome MR analysis to identify candidate biomarkers and evaluate the causal effects of prospective therapeutic targets in DN., Methods: Five DN gene expression datasets were selected from the Gene Expression Omnibus. The robust rank aggregation (RRA) method was used to integrate differentially expressed genes (DEGs) of glomerular samples between patients with DN and controls, followed by functional enrichment analysis. Protein quantitative trait loci were incorporated from seven different proteomic genome-wide association studies, and genetic association data on DN were obtained from FinnGen (3676 cases and 283,456 controls) for two-sample MR analysis. External validation and clinical correlation were also conducted., Results: A total of 82 DEGs (53 upregulated and 29 downregulated) were identified through RRA integrated analysis. The enriched Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathways of the DEGs were significantly enriched in neutrophil degranulation, neutrophil activation, proteoglycan binding, collagen binding, secretory granule lumen, gluconeogenesis, tricarboxylic acid cycle, and pentose phosphate pathways. MR analysis revealed that the genetically predicted levels of MHC class I polypeptide-related sequence B (MICB), granzyme A (GZMA), cathepsin S (CTSS), chloride intracellular channel protein 5, and ficolin-1 (FCN1) were causally associated with DN risk. Expression validation and clinical correlation analysis showed that MICB, GZMA, FCN1, and insulin-like growth factor 1 may participate in the development of DN, and carbonic anhydrase 2 and lipoprotein lipase may play protective roles in patients with DN., Conclusion: Our integrated analysis identified novel biomarkers, including MICB and GZMA, which may help further understand the complicated mechanisms of DN and identify new target pathways for intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fan, Gao and Sun.)