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Abstract Von Hippel-Lindau (VHL) syndrome is a multi-organ neoplastic disease characterized by highly vascular and cystic tumors in the central nervous system (CNS), retina, and visceral lesions, which are mainly caused by germline mutations in VHL. We aimed to detect novel mutations in VHL gene in families with VHL. Here, a large consanguineous four-generation family with variant phenotypes of VHL syndrome was recruited, and its molecular genetics were tested via Sanger sequencing. And various tools and databases were used to predict the variant pathogenicity, frequency, and protein function. Genetic investigation detected a c.351G > A nonsense mutation in VHL that altered the downstream reading frame and created a premature TGA stop signal, resulting in severely truncated pVHL (p.Trp117Ter). This mutation is absent from most public databases, and functional prediction bioinformatic tools demonstrated that this residue is conserved and that this variant is highly likely to be deleterious. The c.315G > A nonsense mutation in VHL is the causal mutation of this kindred that may lead to clear familial aggregation of VHL syndrome because of the dysfunction of the truncated pVHL. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the preliminary clinical outcomes of microwave ablation (MWA)-assisted surgical treatment for large glioma., Materials and Methods: In total, six cases of large glioma (diameter >4 cm) were described. All cases were treated with MWA-assisted surgical resection, which was performed using ultrasound to guide the accurate placement of the antenna in the central region of the tumor. The MWA power was 40-45 W, and 6 min was applied. Changes in the ablation area were observed using intraoperative Doppler ultrasound and contrast-enhanced ultrasound (CEUS). Ten patients treated with surgical resection alone were included in the control group. Data on surgical times (i.e., the time from the incision of the dura to the removal of the tumor), intraoperative blood loss, and complications were recorded., Results: The median patient age was 45 years (range: 36.5-60.3 years). The median lesion diameter was 4.9 cm (range: 4.3-5.8). The microwave power was 40-45 W, and the median ablation time was 240 s (range: 208-297 s). The intra-tumoral vascular flow was significantly reduced after MWA. The median surgical time was shorter (38.5 min [range: 34.3-42.8 min]) and the median intraoperative blood loss was less (400 mL, [range: 400-450 mL]) in the combination treatment group than in the surgery-alone group. During the ablation process, no obvious additional neurological deficits were detected; however, a tube-shaped carbonide was found after the operation., Conclusion: MWA may be a useful complement to conventional techniques for the surgical resection of large glioma.

Objective: To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis., Methods: A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing., Results: MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4)., Conclusion: The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.