PURPOSE The purpose of this study was to develop a framework for analyzing retinal pigment epithelium (RPE) expression profiles from zebrafish eye mutants. METHODS The fish model we used was SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (smarca4), a retinal dystrophic mutant with a previously described retinal phenotype and expression profil...

BACKGROUND Osteoarthritis (OA) is the most common chronic disorder of joints; however, the key genes and transcription factors (TFs) associated with OA are still unclear. Through bioinformatics tools, the study aimed to understand the mechanism of genes associated with the development of OA. METHODS Four gene expression profiling datasets were used to identify differentially expressed genes (...

To determine whether sex differences affect the association between genetic polymorphisms and coronary artery disease (CAD) in the Chinese Han population, we conducted a study comparing the frequency of SH2B3 and SMARCA4 variants in 456 CAD patients (291 men, 165 women) and 685 age-matched controls (385 men, 300 women). Ten single nucleotide polymorphisms (SNPs) in SH2B3 and SMARCA4 were genoty...

BACKGROUND Coronary heart disease (CHD) is the leading cause of death worldwide. Many single-nucleotide polymorphisms (SNPs) are found to be related to the risk of CHD in previous studies. This study investigated whether polymorphism of SMARCA4 gene is associated with CHD. MATERIALS AND METHODS Genotypes at five CHD-relevant SNPs were determined in 456 cases of incident CHD and 685 unaffected...

The tumor suppressor gene, SMARCA4 (or BRG1), which encodes the ATPase component of the chromatin remodeling complex SWI/SNF, is commonly inactivated by mutations and deletions in lung cancer cell lines. However, SMARCA4 alterations appear to be rare in lung primary tumors. Ultra-deep sequencing technologies provide a promising alternative to achieve a sensitivity superior to that of current se...

BACKGROUND Glucocorticoids are used in the curative treatment of acute lymphoblastic leukemia (ALL). Resistance to glucocorticoids is an important adverse prognostic factor in newly diagnosed ALL patients but its mechanism is unknown. Because SWI/SNF complex-mediated chromatin remodeling is required for glucocorticoid transcriptional activity in vitro, we investigated whether expression of subu...

Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requ...

Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodelling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of th...

SMARCA4 chromatin remodelling factor is mutated in 11% of Coffin-Siris syndrome (CSS) patients and in almost all small-cell carcinoma of the ovary hypercalcaemic type (SCCOHT) tumours. Missense mutations with gain-of-function or dominant-negative effects are associated with CSS, whereas inactivating mutations, leading to loss of SMARCA4 expression, have been exclusively found in SCCOHT. We appl...

•Prophylactic oophorectomy can prevent small cell carcinoma of the ovary, hypercalcemic type in carriers of germline SMARCA4 mutations.•Unaffected SMARCA4 mutation carriers who desire children may be best served by oocyte cryopreservation prior to prophylactic oophorectomy.