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Background and aims: Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein‐associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms. Methods: JCAD knockout (JCAD‐KO), liver‐specific JCAD‐KO (Jcad△Hep) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination‐based cell cycle indicator (FUCCI) live‐imaging system was used to visualise the phases of cell cycle. Results: Both global and liver‐specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD‐KO cell line was indicated by a FUCCI live‐imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD‐KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes‐associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle‐associated genes. Conclusion: JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo–YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation. Key Points: JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage.JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle‐associated genes.Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living‐donor liver transplantation. [ABSTRACT FROM AUTHOR]

Hemophilia A (HA, OMIM: 306700) is an X-linked recessive bleeding disorder, caused by defects of the F8 gene which encodes the coagulation factor VIII (FVIII). F8 intron 22 and intron 1 inversion (Inv22 and Inv1) account for ∼45% and 1–5% of severe HA cases, respectively. We herein described an aberrant Inv1 with concomitant large duplication and deletion in a Chinese severe HA patient. Long distance PCR and multiplex PCR were used to detect Inv22 and Inv1. Multiplex ligation-dependent probe amplification (MLPA) was applied to examine exonic duplication and deletion of the F8 gene. Coverage analysis of read depth data from whole-genome sequencing (WGS) was used to analyze the intronic duplication and deletion of the F8 gene. We have identified an aberrant F8 Inv1 in a 1-year-old Chinese severe HA patient showing inversed int1h-1 and normal int1h-2. Coverage analysis of WGS data further illustrated the aberrant Inv1 with concomitant a duplication of 117 kb and a deletion of 1.8 kb. In conclusion, we reported an aberrant Inv1 with concomitant large duplication and deletion in a severe Chinese HA patient. Moreover, WGS provides rapid genetic diagnosis of hereditary disorders with point mutations, deletions, insertions and CNVs. [ABSTRACT FROM AUTHOR]