Ciriaci Nadia, Bertin Lise, Rautou Pierre-Emmanuel
Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France.
Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France.
Hepatology. 2024 Jun 20. doi: 10.1097/HEP.0000000000000973.
Porto-sinusoidal vascular disorder (PSVD) is a rare liver disease. The pathophysiological mechanisms underlying the development of PSVD are unknown. Isolated cases of PSVD associated with gene mutations have been reported, but no overview is available. Therefore, we performed an extensive literature search to provide a comprehensive overview of gene mutations associated with PSVD. We identified 34 genes and 1 chromosomal abnormality associated with PSVD in the literature, and we describe here 1 additional gene mutation ( TBL1XR1 mutation, leading to Pierpont syndrome). These gene mutations are associated either with extrahepatic organ involvement as part of syndromes (Adams-Oliver, telomere biology disorders, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, immune deficiencies, cystic fibrosis, cystinosis, Williams-Beuren, Turner, Pierpont) or with isolated PSVD ( KCNN3 , DGUOK , FOPV , GIMAP5 , FCHSD1 , TRMT5 , HRG gene mutations). Most of the cases were revealed by signs or complications of portal hypertension. When analyzing the cell types in which these genes are expressed, we found that these genes are predominantly expressed in immune cells, suggesting that these cells may play a more important role in the development of PSVD than previously thought. In addition, pathway analyses suggested that there may be 2 types of PSVD associated with gene mutations: those resulting directly from morphogenetic abnormalities and those secondary to immune changes.
肝窦状隙血管疾病（PSVD）是一种罕见的肝脏疾病。PSVD发生的病理生理机制尚不清楚。已有孤立的PSVD病例与基因突变相关的报道，但尚无综述。因此，我们进行了广泛的文献检索，以全面概述与PSVD相关的基因突变。我们在文献中确定了34个基因和1种与PSVD相关的染色体异常，并且在此描述另外1种基因突变（TBL1XR1突变，导致皮尔庞特综合征）。这些基因突变要么与作为综合征一部分的肝外器官受累有关（亚当斯-奥利弗综合征、端粒生物学障碍、伴有脑白质病和全身表现的视网膜血管病变、免疫缺陷、囊性纤维化、胱氨酸病、威廉姆斯-贝伦综合征、特纳综合征、皮尔庞特综合征），要么与孤立性PSVD有关（KCNN3、DGUOK、FOPV、GIMAP5、FCHSD1、TRMT5、HRG基因突变）。大多数病例由门静脉高压的体征或并发症发现。在分析这些基因表达的细胞类型时，我们发现这些基因主要在免疫细胞中表达，这表明这些细胞在PSVD的发生中可能比以前认为的发挥更重要的作用。此外，通路分析表明，可能存在2种与基因突变相关的PSVD：直接由形态发生异常导致的和继发于免疫变化的。
