RESUMEN
The most common genetic backgrounds of hereditary paraganglioma and pheochromocytoma (PPGL) are SDHx germline mutations. Given the fact that the immunohistochemistry (IHC) result for SDHB is always negative regardless of the type of SDHx mutation, we aimed to evaluate the efficacy of using SDHB IHC for screening SDHx mutations in PPGL cases. In total, 52 patients who underwent surgery for PPGL treatment between 2006 and 2020 and underwent genetic analysis at diagnosis were included. Tissue microarrays (TMAs) were constructed with PPGL tissues and IHC for SDHB was performed on TMA sections. All 10 patients with SDHB-negative IHC contained SDHB or SDHD mutations. The genetic test results of patients with SDHB-weakly positive IHC varied (one SDHB, two RET, one VHL, and three unknown gene mutations). There were no SDHx mutations in the SDHB-positive IHC group. Six patients with weakly positive SDHB IHC with primarily unknown genetic status were re-called and underwent next-generation sequencing. None of them had SDHx mutations. In conclusion, SDHB-negative IHC is a cost-effective and reliable method to predict SDHx mutations. However, in the case of weakly positive SDHB staining, an additional gene study should be considered.
RESUMEN
BACKGROUND: Congenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT. RESULTS: Twenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or immunohistochemical studies. We first identified 269 genes as the DEGs in CMT. Gene ontology enrichment analysis revealed that the main function of the DEGs is for extracellular region part during developmental processes. Five CMT-related protein network modules were identified, which showed that the important pathway is fibrosis related with collagen and elastin fibrillogenesis with an evidence of DNA repair mechanism. Interestingly, the expression levels of the 8 DEGs called CMT signature genes whose mRNA expression was double-confirmed by quantitative real time PCR showed good correlation with the severity of CMT which was measured with the pre-operational MRI images (R2 ranging from 0.82 to 0.21). Moreover, the protein expressions of ELN, ASPN and CHD3 which were identified from the CMT-related protein network modules demonstrated the differential expression between the CMT and normal SCM. CONCLUSIONS: We here provided an integrative analysis of CMT from gene expression to clinical significance, which showed good correlation with clinical severity of CMT. Furthermore, the CMT-related protein network modules were identified, which provided more in-depth understanding of pathophysiology of CMT.
