Humans ; Ulcer ; Intestinal Diseases ; Myelodysplastic Syndromes/genetics* ; Trisomy/genetics* ; Behcet Syndrome

Objective: To retrospectively investigate the clinical data, radiological characteristics, treatment, and outcome of patients with parenchymal neuro-Behcet's disease (P-NBD) with particular emphasis on dizziness. Methods: This was a cross-sectional study of clinical data from 25 patients with a confirmed diagnosis of P-NBD who were admitted to the Department of Neurology of the First Medical Center of Chinese People's Liberation Army General Hospital between 2010 and 2022. The median age of the population was 37 years (range: 17-85 years). Clinical data were retrospectively analyzed, including gender, age of onset, disease duration, clinical manifestations, serum immune indicators, cerebrospinal fluid (CSF) routine biochemical and cytokine levels, cranial and spinal magnetic resonance imaging (MRI) findings, treatment, and outcome. Results: The majority of patients were male (16 cases; 64.0%), the mean age of onset was (28±14) (range: 4-58 years), and the disease course was acute or subacute. Fever was the most common clinical presentation, and the complaint of dizziness was not uncommon (8/25 patients). Analysis of serum immune indices, including complement (C3 and C4), erythrocyte sedimentation rate, interleukin-1 (IL-1), IL-6, IL-8 and tumor necrotic factor-alpha were abnormal in 80.0% of patients (20/25). Most of the 16/25 patients who underwent lumbar puncture tests had normal intracranial pressure and increased CSF white cell count and protein [median values were 44 (15-380) ×10⁶/L and 0.73 (0.49-2.81) g/L, respectively]. Of the five patients who underwent CSF cytokine tests, four patients had abnormal results; of these, an elevated level of IL-6 was most common, followed by IL-1 and IL-8. The most common site of involvement in cranial MRI was the brainstem and basal ganglia (60.0% respectively), followed by white matter (48.0%) and the cortex (44.0%). Nine cases (36.0%) showed lesions with enhancement and six cases (24.0%) showed mass-like lesions. Three patients (12.0%) patients had lesions in the spinal cord, most frequently in the thoracic cord. All patients received immunological intervention therapy; during follow up, the majority had a favorable outcome. Conclusions: P-NBD is an autoimmune disease with multiple system involvement and diverse clinical manifestations. The symptom of dizziness is not uncommon and can be easily ignored. Early treatment with immunotherapy is important and can improve the outcome of these patients.
Humans ; Male ; Female ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Behcet Syndrome/diagnosis* ; Interleukin-6 ; Retrospective Studies ; Cross-Sectional Studies ; Interleukin-8 ; Magnetic Resonance Imaging ; Neurology

OBJECTIVE: To analyze the clinical manifestations and causative gene variants of the choroideremia patients, and to help the patients bedifferential diagnosed by whole exome sequencing and provide theoretical basis for their genetic counseling. METHODS: Clinical data of 3 families were collected and genomic DNA was extracted respectively from peripheral blood of patients and related subjects. Exome targeted sequencing was used to screen suspicious gene mutations. Sanger sequencing and quantitative PCR were used to verify the candidate mutations and investigate the mutation carrying status of other members of the family. The candidate mutations were searched through HGMD and PubMed databases for the pathogenicity reports, and the pathogenicity of candidate mutations was judged according to a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. RESULTS: The proband of family 1 is c.1584_1587del (p.Val529Hisfs*6) variant hemizygote, whose daughter carries c.1584_1587del (p.Val529Hisfs*6) heterozygous variation. The proband of family 2 is a hemizygote with deletion of exons 10 to 15 (E10-15del), and her mother and sister carry the E10-15del heterozygous variation. In family 3, the proband is c.544delT (p.Cys182Valfs*14) variant hemizygote, and his mother is c.544delT (p.Cys182Valfs*14) heterozygote, but the father do not detect this variant. All the 3 families were detected pathogenic gene variations of CHM, two of which were known pathogenic variation and one of which was novel CHM gene c.544delT (p.C182Vfs*14) in this study. The c.544delT frameshift mutation of CHM gene can lead to the premature termination of the product protein translation and nonfunctioning protein. It is a pathogenic mutation according to ACMG guidelines. CONCLUSION The findings of this study expand the gene variation spectrum of choroideremia.
Choroideremia/genetics* ; Female ; Heterozygote ; Humans ; Mutation ; Pedigree ; Whole Exome Sequencing

Chromosome Deletion ; Humans ; Kidney Neoplasms ; WAGR Syndrome/genetics* ; Wilms Tumor

Objectives: We presented a case of bilateral iridocorneal endothelial (ICE) syndrome with secondary glaucoma and discussed its clinical presentation and management. Study design: This is a case report. Results: A 12-year old female consulted for a one-year history of progressive blurring of vision in both eyes associated with abnormal pupils and occasional eye pain. Polycoria, shallow anterior chambers, increased intraocular pressures (IOP), areas of closed angles on gonioscopy, and increased cup-to-disc ratio in both eyes indicative of ICE syndrome were present. Management included anti-glaucoma medications and implantation of glaucoma drainage devices (GDD). Conclusion Early detection with regular follow-ups leading to prompt management of the ICE syndrome are necessary. IOP control may be challenging due to the nature of the disease and may require multiple surgeries including GDD implantation to achieve successful outcomes. Early use of GDD may be beneficial for pediatric patients with ICE and glaucoma, and may require additional surgeries to adequately manage the IOP.
Iridocorneal Endothelial Syndrome

Humans ; Heart Ventricles ; Behcet Syndrome/complications* ; Heart ; Heart Diseases ; Ventricular Dysfunction, Left

Humans ; Behcet Syndrome/diagnostic imaging*

More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gα_q/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gα_q/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gα_q/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
Humans ; Mice ; Animals ; Lipoylation ; NIH 3T3 Cells ; Uveal Neoplasms/genetics* ; Melanoma/genetics* ; Cell Proliferation ; Proto-Oncogene Proteins c-bcl-2 ; GTP-Binding Protein alpha Subunits, Gq-G11/genetics*

Behçet's disease (BD) is a systemic vasculitis characterized by recurrent acute vascular inflammation. There is currently limited epidemiological data in Southeast Asia. We discuss a 26-year-old woman who came to our institution for recurrent vulvar abscesses for a year. Physical examination showed labial, tongue, and vulvar ulcers. Pathergy test was negative and biopsy done were unremarkable . We diagnosed her clinically as a case of Behçet’s disease. We started her on colchicine 0.6 mg once daily and educated her on skin, oral, and perineal hygiene. On follow-up after one month, she noted resolution of her lesions. However, symptoms recurred in the last three months after discontinuing treatment. We used telemedicine to communicate due to the COVID-19 pandemic and lockdown, advising her to continue her medication. Timely diagnosis is essential in order to provide symptomatic relief and enhance patient education.
Behcet Syndrome ; Ulcer ; Vasculitis

Humans ; Panuveitis/etiology* ; Retinal Detachment/etiology* ; Typhoid Fever/diagnosis* ; Visual Acuity