Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Renal vein thrombosis (RVT) is a rare vascular complication that occurs after renal transplantation and usually results in irreversible kidney damage and graft loss. We report the case of a patient who underwent right iliac fossa allogeneic kidney transplantation and developed RVT combined with ipsilateral thrombosis from the popliteal to the femoral veins, with extension to the common iliac veins, 4 months after transplantation. Under unfractionated heparin anticoagulation, an Aegisy (Life Tech Scientific Co., Ltd., Shenzhen, China) vena cava filter was placed to prevent pulmonary embolism. Percutaneous mechanical thrombectomy combined with balloon angioplasty was performed to aspirate the thrombus and successfully dilate the narrow venous lumen. The patient's renal function was restored postoperatively. Ultrasonography showed the allograft and ipsilateral lower extremity deep veins to be fluent and patent. To conclude, in patients with RVT after renal transplantation, percutaneous mechanical thrombectomy in conjunction with balloon angioplasty can be performed with desirable outcomes and no severe adverse effects. This method reduces the risk of bleeding from exposure to systemic intravenous thrombolysis and avoids surgery-associated trauma.

Background Superior mesenteric vein (SMV) thrombosis is a rare intestinal ischemic disease. The clinical manifestations of patients differ, and most experience gastrointestinal symptoms. Case summary A 45-year-old female patient presented with persistent abdominal pain and abnormal vaginal bleeding for 7 days. A physical examination revealed significant abdominal tenderness with positive rebound tenderness. A laboratory examination revealed a white blood cell count of 27 × 10 9 /l, hemoglobin level of 52 g/L, and D-dimer of 4.54 mg/l. Enhanced computed tomography revealed a thickening and swelling of the jejunum and ileum in the left upper quadrant and portal vein. Filling defects in the main lumen and branch lumen suggested the possibility of portal vein and superior mesenteric vein thrombosis. Symptoms improved after treatment with low-molecular-weight heparin and warfarin. One month later, the patient developed occasional dull pain in the left lower quadrant, with long strips of discharge. An electronic colonoscopy revealed avascular necrosis and tissue exfoliation of the intestinal mucosa. After the continuation of warfarin therapy, the abdominal pain resolved. Five months later, the patient experienced recurrent abdominal pain and vomiting. A physical examination revealed a blood pressure of 75/49 mm Hg. An incomplete ileus with the portal and superior mesenteric vein thrombosis was diagnosed, partial jejunectomy and gastrointestinal bypass anastomosis were performed, and warfarin was continued postoperatively. Conclusion The intestinal mucosal shedding observed, in this case, was caused by SMV thrombosis, which enriched the clinical manifestations of the disease and provided a new basis for the clinical diagnosis of SMV thrombosis.

Background Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. Methods Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. Results The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. Conclusions The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

Background:The analgesic effect produced by the intra-arterial injection of lidocaine in patients undergoing uterine artery embolization has been proven to be safe and effective. Nevertheless, a significant degree of pain is typically experienced after the operation, and pain management is crucial. Methylprednisolone, which provides an anti-inflammatory effect, is widely used in the treatment of several diseases. To date, methylprednisolone has not been used after uterine artery embolization.Methods:A total of 131 patients with uterine leiomyoma were retrospectively enrolled. Forty-five patients (control group) were treated with embolized microspheres for bilateral uterine artery embolization. Fifty (study group) and 36 (lidocaine group) patients were administered lidocaine mixed with embolized microspheres during embolization, and in addition, the study group was administered methylprednisolone. Completed pain scales at different time points during surgery were obtained from patients undergoing uterine artery embolization. Efficacy against pain was evaluated by comparing the pain score, inflammatory index, and use of sufentanil within 24 h followed by a Kruskal-Wallis Test and a least significant difference post-hoc analysis.Results:The postoperative pain scores at 1, 4, and 7 h after uterine artery embolization in the study group (3.08 ± 2.09, 2.46 ± 1.93, and 2.38 ± 1.85, respectively) were significantly lower than those in the control group (4.84 ± 2.36, 4.16 ± 1.87, and 3.56 ± 1.93, respectively) and the lidocaine group (3.50 ± 2.10, 3.30 ± 1.88, and 3.28 ± 1.89, respectively). At the first 24 h after embolization, the total usage of sufentanil in the study group (31.4 ± 4.16) was significantly lower than those in the control group (45.7 ± 6.51) and the lidocaine group (38.3 ± 6.25). At 1 and 4 h, the pain scores of the lidocaine group were significantly lower than those of the control group. In addition, at the first 24 h after embolization, the total usage of sufentanil in the lidocaine group was significantly lower than that in the control group.Conclusion:Lidocaine in combination with methylprednisolone can significantly alleviate pain and reduce the usage of sufentanil after bilateral uterine artery embolization. Thus, methylprednisolone is a recommended addition to the therapeutic regimen after embolization.