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SAPHO syndrome is a rare chronic inflammatory disease which is characterized by the comprehensive manifestations of bone, joint, and skin. However, little is known about the pathogenesis of SAPHO syndrome. A genome-wide association study (GWAS) of 49 patients and 121 control subjects have primarily focused on identification of common genetic variants associated with SAPHO, the data were analyzed by classical multiple logistic regression. Later, GWAS findings were further validated using whole exome sequencing (WES) in 16 patients and 15 controls to identify potentially functional pathways involved in SAPHO pathogenesis. In general, 40588 SNPs in genomic regions were associated with P < 0.05 after filter process, only 9 SNPs meet the expected cut-off P-value, however, none of them had association with SAPHO syndrome based on published literatures. And then, 15 pathways were found involved in SAPHO pathogenesis, of them, 6 pathways including osteoclast differentiation, bacterial invasion of epithelial cells, et al., had strong association with skin, osteoarticular manifestations of SAPHO or inflammatory reaction based published research. This study identified aberrant osteoclast differentiation and other pathways were involved in SAPHO syndrome. This finding may give insight into the understanding of pathogenic genes of SAPHO and provide the basis for SAPHO research and treatment.

Genetic variation in specific transcription factors during heart formation may lead to congenital heart disease (CHD) or even miscarriage. The aim of the present study was to identify CHD-associated genes using next generation sequencing (NGS). The whole exome DNA sequence was obtained from a stillborn fetus diagnosed with tricuspid atresia and complete transposition of the great arteries using high-throughput sequencing methods. Subsequently, genetic variants of CHD-associated genes were selected and verified in 215 non-syndromic CHD patients and 249 healthy control subjects using polymerase chain reaction combined with Sanger sequencing. Genetic variants of previously reported CHD-inducing genes, such as cysteine rich with EGF like domains 1 and cbp/p300-interacting transactivator with Glu/Asp rich carboxy-terminal domain 2, were discovered through the NGS analysis. In addition, a novel non-synonymous mutation of the iroquois homeobox 1 (IRX1) gene (p.Gln240Glu) was identified. A total of three non-synonymous mutations (p.Gln240Glu, p.Ser298Asn and p.Ala381Glu) of the IRX1 gene were verified in 215 non-syndromic CHD patients, but not in 249 healthy volunteers. The results demonstrated that NGS is a powerful tool to study the etiology of CHD. In addition, the results suggest that genetic variants of the IRX1 gene may contribute to the pathogenesis of CHD. [ABSTRACT FROM AUTHOR]

Ventricular septal defect (VSD) is the most common type of congenital heart disease (CHD). The single gene mutations or absences that contribute to VSD development are well established; however, the aim of the present study was to measure gene expression variation between VSDs and normal fetal myocardial tissue. TWIST1, an important tumor biomarker, is a basic helix-loop-helix transcription factor that regulates cell proliferation, migration and differentiation in embryonic development and transformed tumor cells. Although growing evidence demonstrates that TWIST1 participates in a variety of human neoplastic diseases, the role of TWIST1 in VSD has remained elusive. Twenty-six VSD fetal myocardial tissue samples and 12 normal samples at matched gestational weeks (22-28 weeks) were included in the present study. Using reverse transcription quantitative polymerase chain reaction (PCR) and real-time PCR, it was demonstrated that TWIST1 mRNA was reduced by almost two-fold in the VSD samples compared with the normal samples. Western blot analysis also revealed that TWIST1 expression was decreased by ~three-fold (P=0.001) in the VSD samples compared with that in the normal samples. Of note, five complete ventricular (also called functionally univentricular or single ventricular) septal ageneses were identified among the specimens. For the five complete ventricular septal agenesis samples, similar results to those for other VSD fetal myocardial tissues were obtained. In conclusion, the results of the present study showed that TWIST1 mRNA and protein levels were reduced in VSDs. The present study was the first, to the best of our knowledge, to report that TWIST1 is not only a tumor biomarker, but may also be involved in the pathogenesis of VSD. [ABSTRACT FROM AUTHOR]