UNASSIGNED: Genetic and acquired risk factors are fundamental to developing venous thromboembolism. Autosomal dominant protein S deficiency caused by pathogenic mutations in the PROS1 gene is a well-known risk factor for thrombophilia.
UNASSIGNED: We report a 30-year-old male patient who presented to the hospital with portal vein thrombosis. The patient had a history of abdominal pain for one month. Abdominal vascular CT showed venous thrombosis in the portal vein and superior mesenteric vein. He was diagnosed with \"portal and superior mesenteric vein thrombosis, small bowel obstruction and necrosis, acute upper gastrointestinal bleeding (UGIB), hemorrhagic shock.\" Serum protein S levels were decreased, and gene sequencing revealed a heterozygous missense mutation in PROS1, c.1571T > G (p.Leu584Arg). The patient received anticoagulation therapy with Enoxaparin Sodium and rivaroxaban, transjugular intrahepatic portosystemic shunt (TIPS), and ICU treatments. Although the patient had a severe bleeding event during anticoagulation therapy, he recovered well after active treatment and dynamic monitoring of anti-Xa.
UNASSIGNED: Hereditary protein S deficiency caused by a mutation in the PROS1 gene is the genetic basis of this patient, and Enoxaparin Sodium and rivaroxaban have been shown to be highly effective.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by motile ciliary dysfunction and impaired ultrastructure. Despite numerous studies, the genetic basis for about 30% of PCD cases remains to be elucidated. Here, we present the identification and functional analysis of two novel mutations in the gene encoding coiled-coil domain-containing protein 40 (CCDC40), which are found in a familial case of PCD. These novel CCDC40 mutations, NM_017950.4: c.2236-2delA and c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs), were identified by whole-exome sequencing (WES). Sanger sequencing was then performed to confirm the WES results and determine the CCDC40 gene sequences of the proband\'s parents. The c.2042_2046delTCACA mutation disrupts the reading frame of the protein and is therefore predicted to produce a non-functional protein. Using a minigene assay with the pcDNA3.1(+) plasmid, we further investigated the potential pathogenic effects of the c.2236-2delA mutation and found that this mutation leads to formation of a truncated protein via splicing disruption. Thus, in summary, we identified two mutations of the CCDC40 gene that can be considered pathogenic compound heterozygous mutations in a case of familial PCD, thereby expanding the known mutational spectrum of the CCDC40 gene in this disease.

Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin.
This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality.
The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.