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http://dx.doi.org/10.1097/HS9.0000000000000774 | DOI Listing |
Nat Commun
September 2025
Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China.
ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare genetic disease caused by variants in alpha-kinase 1 (ALPK1) resulting in downstream pro-inflammatory signaling mediated by the TIFA/TRAF6/NF-κB pathway. Here, we report the design of an ALPK1 inhibitor, DF-003, with pharmacokinetic properties suitable for daily oral dosing. In biochemical assays, DF-003 potently inhibits human ALPK1 (IC = 1.
View Article and Find Full Text PDFAm J Hum Genet
September 2025
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam 3000 CA, the Netherlands.
Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this domain result in a distinctive cortical and brain stem malformation.
View Article and Find Full Text PDFStem Cell Res
September 2025
Department of Cardiology, Affiliated Hospital of Jining Medical University, Shandong, China; Shandong Provincial Key Medical and Health Discipline of Cardiology Affiliated Hospital of Jining Medical University, Shandong, China; Key Laboratory of Cell and Biomedical Technology of Shandong Province, C
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary infiltrative cardiomyopathy characterized by fibrofatty replacement of the right ventricular myocardium, which may extend to the left ventricle in the advanced stages. Clinically, the condition is commonly associated with right ventricular dilation, malignant arrhythmias, and an increased risk of sudden cardiac death. In this study, we successfully established induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of ARVC patients carrying a heterozygous LMNA gene mutation (c.
View Article and Find Full Text PDFTurk J Pediatr
September 2025
Division of Pediatric Rheumatology, Department of Pediatrics, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Türkiye.
Background: We aimed to document childhood onset mevalonate kinase deficiency (MKD) and to explore treatment responses and diagnostic challenges in regions endemic to familial Mediterranean fever (FMF).
Methods: This retrospective study included patients under 18 years of age, diagnosed with MKD and followed for at least six months at the pediatric rheumatology department of Istanbul University - Cerrahpaşa Medical Faculty between 2016 and 2024.
Results: Of 33 patients, 51.
Introduction: Genetic analysis is essential for diagnosing, treating, and predicting complications in neonatal diabetes mellitus (NDM) but is unavailable in some regions. Sulfonylureas are effective for NDM caused by KCNJ11 or ABCC8 mutations, which are among the most common genetic causes, therefore they are often given before genetic testing. Unfortunately, in certain ethnicities, this mutation rarely occurs.
View Article and Find Full Text PDF