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- Title
Mutations in the novel gene <italic>FOPV</italic> are associated with familial autosomal dominant and non‐familial obliterative portal venopathy.
- Authors
Besmond, Claude; Hubert, Laurence; Poirier, Karine; Valla, Dominique; Grosse, Brigitte; Gonzales, Emmanuel; Jacquemin, Emmanuel; Guettier, Catherine; Bernard, Olivier
- Abstract
Abstract: Background & Aims: Obliterative portal venopathy (OPV) is characterized by lesions of portal vein intrahepatic branches and is thought to be responsible for many cases of portal hypertension in the absence of cirrhosis or obstruction of large portal or hepatic veins. In most cases the cause of OPV remains unknown. The aim was to identify a candidate gene of OPV. Methods: Whole exome sequencing was performed in two families, including 6 patients with OPV. Identified mutations were confirmed by Sanger sequencing and expression of candidate gene transcript was studied by real time qPCR in human tissues. Results: In both families, no mutations were identified in genes previously reported to be associated with OPV. In each family, we identified a heterozygous mutation (c.1783G>A, p.Gly595Arg and c.4895C>T, p.Thr1632Ile) in a novel gene located on chromosome 4, that we called <italic>FOPV</italic> (Familial Obliterative Portal Venopathy), and having a cDNA coding for 1793 amino acids. The <italic>FOPV</italic> mutations segregated with the disease in families and the pattern of inheritance was suggestive of autosomal dominant inherited OPV, with incomplete penetrance and variable expressivity. In silico analysis predicted a deleterious effect of each mutant and mutations concerned highly conserved amino acids in mammals. A deleterious heterozygous <italic>FOPV</italic> missense mutation (c.4244T>C, p.Phe1415Ser) was also identified in a patient with non‐familial OPV. Expression study in liver veins showed that <italic>FOPV</italic> transcript was mainly expressed in intrahepatic portal vein. Conclusions: This report suggests that <italic>FOPV</italic> mutations may have a pathogenic role in some cases of familial and non‐familial OPV.
- Subjects
PORTAL vein diseases; GENETIC mutation; HYPERTENSION; NUCLEOTIDE sequencing; EXOMES; POLYMERASE chain reaction
- Publication
Liver International, 2018, Vol 38, Issue 2, p358
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.13547