Rationale: Hypohidrotic ectodermal dysplasia (HED) is a rare inherited disorder characterized by hypohidrosis, hypotrichosis, and hypodontia. Most cases are caused by mutations in the EDA signaling pathway, whereas TP63-related HED is extremely rare. To our knowledge, this is the first reported case of HED caused by a novel TP63 mutation presenting with a pathological femoral neck fracture. Patient concerns: A 31-year-old woman presented with progressive left hip pain and inability to bear weight for 2 weeks without a history of trauma. She had a lifelong history of hypohidrosis, heat intolerance, sparse hair, hypodontia, dry skin, and nail abnormalities. Diagnoses: Physical examination and radiographs revealed a displaced femoral neck fracture. Laboratory investigations demonstrated severe anemia, end-stage renal disease, secondary hyperparathyroidism, vitamin D deficiency, and osteoporosis. Whole exome sequencing identified a previously unreported heterozygous TP63 frameshift mutation (NM_001114982, c.1092_1093del, p.Asn364fs). Based on the clinical manifestations, laboratory findings, and genetic testing results, the patient was diagnosed with HED, pathological femoral neck fracture, end-stage renal disease, secondary hyperparathyroidism, osteoporosis, and severe anemia. Interventions: After correction of anemia and electrolyte imbalance by hemodialysis and blood transfusion, the patient underwent uncemented bipolar hemiarthroplasty. Outcomes: She began partial weight-bearing ambulation on postoperative day 3 and was discharged on postoperative day 6. Lessons: This case expands the mutational and phenotypic spectrum of TP63-associated HED by describing a previously unreported mutation presenting with a pathological femoral neck fracture and end-stage renal disease. It highlights the importance of early diagnosis, comprehensive genetic testing, multidisciplinary management, and regular follow-up for patients with HED.
Guanghua Liang, Xiang-Ning Meng, Talante Juma et al.· Medicine· 0 citations
BACKGROUND
This study focuses on exploring the co-morbid mechanisms by which Bisphenol A (BPA) induces non-alcoholic fatty liver disease (NAFLD) and osteoarthritis (OA).
METHOD
This study identified potential BPA targets utilizing the SwissTargetPrediction database. These targets were integrated with genes associated with NAFLD and OA, which were screened via Weighted Gene Co-expression Network Analysis and differential gene expression analysis. To elucidate the underlying biological mechanisms, functional enrichment and immune infiltration analyses were conducted. Core genes associated with comorbidity were pinpointed via machine learning. The interactions and cellular localization were further validated by molecular docking, molecular dynamics simulations, and single-cell transcriptomics. Finally, in vitro experiments were employed to verify the effects on chondrocyte function, and hepatic lipid metabolism.
RESULTS
Functional enrichment analysis indicates that BPA-induced NAFLD and OA comorbidity pathways are enriched in muscle cell proliferation, DNA metabolism, and inflammation pathways. RHOB has been identified as a core gene, participating in disease progression by regulating signaling pathways such as Hippo and IL-17. Single-cell sequencing revealed that RHOB is primarily expressed in hepatocytes and cholangiocytes in NAFLD, while enriching in HomC and EC cell clusters in OA. In vitro experiments confirmed that BPA exposure suppresses RHOB expression, thereby promoting lipid accumulation in hepatocytes and impairing chondrocyte function. Concurrently, rescue experiments demonstrated that its overexpression significantly reversed these pathological states.
CONCLUSION
BPA exposure drives the co-morbidity of OA and NAFLD by inhibiting RHOB. Consequently, limiting BPA exposure or modulating the RHOB pathway represents a viable approach for intervening in related diseases.
