Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by aggressive osteolysis associated with progressive nephropathy. The early clinical presentation can mimic polyarticular juvenile idiopathic arthritis. Since 2012, MAFB mutations have been discovered in all MCTO patients. Therefore, the early diagnosis can be made based on genetic confirmation. We report the clinical manifestation of mineral bone disease and the molecular genetic study of a Thai female adolescent with MCTO. She presented with end-stage renal disease, bilateral wrist and ankle joint deformities, and subtle facial dysmorphic features. We identified a heterozygous missense MAFB mutation at nucleotide 197 from C to G (NM_005461.4; c.197C>G), predicting the change of amino acid at codon 66 from serine to cysteine (p.Ser66Cys), and the mutation was absent in the parents, indicating a de novo mutation. This report confirms the previous link between MAFB mutation and MCTO. Her unexplained hypercalcemia after a regular dose of calcium and active vitamin D supported an important role of MafB in the negative regulation of RANKL-mediated osteoclast differentiation. Therefore, we would encourage the physicians who take care of MCTO patients to closely monitor serum calcium level and perform a genetic study as a part of the management and investigation.

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CD19 chimeric antigen receptor (CAR) T-cells have demonstrated remarkable outcomes in B-cell malignancies. Recently, the novel CD19CAR-T cells incorporated with B-cell costimulatory molecules of CD79A/CD40 demonstrated superior antitumor activity in the B-cell lymphoma model compared with CD28 or 4-1BB. Here, we investigated the intrinsic transcriptional gene underlying the functional advantage of CD19.79A.40z CAR-T cells following CD19 antigen exposure using transcriptome analysis compared to CD28 or 4-1BB. Notably, CD19.79A.40z CAR-T cells up-regulated genes involved in T-cell activation, T-cell proliferation, and NF-κB signaling, whereas down-regulated genes associated with T-cell exhaustion and apoptosis. Interestingly, CD19.79A.40z CAR- and CD19.BBz CAR-T cells were enriched in almost similar pathways. Furthermore, gene set enrichment analysis demonstrated the enrichment of genes, which were previously identified to correlate with T-cell proliferation, interferon signaling pathway, and naïve and memory T-cell signatures, and down-regulated T-cell exhaustion genes in CD79A/CD40, compared with the T-cell costimulatory domain. The CD19.79A.40z CAR-T cells also up-regulated genes related to glycolysis and fatty acid metabolism, which are necessary to drive T-cell proliferation and differentiation compared with conventional CD19CAR-T cells. Our study provides a comprehensive insight into the understanding of gene signatures that potentiates the superior antitumor functions by CD19CAR-T cells incorporated with the CD79A/CD40 costimulatory domain.

Background: BRCA1 and BRCA2 genes are known to increase breast cancer's lifetime risk. Early identification of women with this inherited risk can potentially reduce the risk of breast and/or ovarian cancer and, together with early screening, decrease the mortality rate. Objective: This study explored the frequency and distribution of genetic variants in consecutive cases of breast cancer in Narathiwat province, one of the three provinces in the southernmost Thai border. Material & Method: A series of 64 consecutive breast cancer patients who underwent treatment in two general hospitals in the province during the period from the year 2021 to 2022. Genotyping studies were performed using a whole exome sequencing platform. Moderate to high penetrance variants recommended by the National Comprehensive Cancer Network (NCCN) guidelines 2022 (ATM,

Patient: Female, 2-year-old Final Diagnosis: Juvenile hyaline fibromatosis Symptoms: Multiple painless soft tissue masses affecting the ears • forehead • scalp Medication: — Clinical Procedure: Excision biopsy • surgery removal Specialty: Pediatrics and Neonatology • Surgery Objective: Rare disease Background: Juvenile hyaline fibromatosis is a rare autosomal recessive disorder with unknown prevalence characterized by abnormal development of hyalinized fibrous tissue usually in the skin, mucosa, bone, and often the internal organs. Here, we report the case of a 7-year-old girl from a family with ANTXR2 mutation confirming JHF. Case Report: The girl presented with multiple painless soft-tissue swellings affecting the ears, forehead, and scalp. Excisional biopsies of the masses reported positive immunohistochemical staining for collagen type VI in the extracellular matrix area, which indicated collagen VI accumulation. Genetic analysis was performed using whole-exome sequencing. The variants were further validated using Sanger sequencing in trio-based approach. We identified a novel mutation, c.1273_1293delinsTCTTGTGGGTTTGGCT in exon 15 of ANTXR2 gene, leading to a frame-shift of the amino acid from codon 425 to all the rest of the amino acid chain (p.Pro425Serfs). The change of an encoded protein interrupted lysosome-mediated degradation of collagen VI. This finding was compatible with her parents whose genetic tests were both positive for the same heterogenous deletion/insertion mutation. The patient was treated with surgical excision of the tumor masses, which had to be repeated several times due to recurrences. Conclusions: This novel mutation in exon 15 of the ANTXR2 gene may help improve understanding of genotype-phenotype correlations for this syndrome and provide the basis for diagnostic testing. A multidisciplinary team approach including genetic molecular testing is required for an accurate diagnosis and management of JHF for conducting genetic counseling for affected families as a part of holistic management.