ObjectiveTo investigate research advance on the value of B-type RAF kinase (BRAF) gene mutation assisted diagnosis of papillary thyroid cancer (PTC) in thyroid nodule.MethodThe recent literatures on the BRAF gene mutation and its combination with fine needle aspiration cytology (FNAC) in the diagnosis of benign and malignant thyroid nodules and PTC were collected and reviewed.ResultsThe BRAFV600E gene mutation was the most common type of gene mutation in the genetic molecule of PTC. The combination of the FNAC and BRAF gene mutation detection could improve the diagnostic value of the benign and malignant thyroid nodules, especially the diagnostic accuracy of PTC. However, the negative detection of BRAF gene mutation did not rule out the possibility of PTC. It still remained controversial that the detection of BRAF gene mutation could differentiate between the benign and malignant thyroid nodules.ConclusionsBRAF gene mutation detection has different diagnostic values in different types of thyroid nodules. It has considerable diagnostic value in thyroid nodules with high BRAF mutation incidence (suspicious for malignancy, undetermined significance or follicular lesion of undetermined significance nodules) while presents false negative result in thyroid nodule with very low mutation incidence category to a large extent. BRAF gene detection might become a specific diagnostic molecular marker to promote diagnosis accuracy of PTC.
Objective
To investigate clinicopathologic features, pathogenesis, and diagnosis and treatment of hereditary pancreatitis (HP).
Method
The relevant literatures on HP research in recent years were searched and reviewed.
Results
The HP was similar to the pancreatitis caused by the cholelithiasis, excessive alcohol consumption, hyperlipidemia, etc. in the histomorphology, function, and clinical manifestations and it was difficult to be distinguished. However, HP was different from the other types of chronic pancreatitis due to its early onset, familial, and high risk of pancreatic cancer. The HP was mainly caused by the PRSS1 mutations, and its mutation types mainly included the R122H, N29I, A16V, K23R, etc., among which the R122H and N29I were the two most common types of mutations. There was no specific treatment for the HP. The principles of treatment of HP were similar to the pancreatitist caused by other etiologies, including the nutritional support, blood sugar control, analgesia, etc.. In addition to the medical treatment, the surgical intervention was also the important means for the treatment of HP, including the pancreatic partial resection, total pancreatectomy or total pancreatectomy combined with islet cell autografting.
Conclusions
HP is an autosomal dominant hereditary disease characterized by recurrent attacks of pancreatitis. Relevant gene tests could be performed for patient with highly suspected HP. It faces great challenges in treatment of HP. Pathogenesis of HP needs to be constantly explored and experimental study of multicenter and large sample needs to be further studied in order to determine its best treatment strategy.
Mutations in optic atrophy (OPA) genes can lead to a similar phenotype, namely optic atrophy, which can manifest as isolated optic atrophy or be accompanied by other systemic symptoms, mostly related to the nervous system. Currently, a total of 13 OPA genes have been discovered, covering a variety of inheritance patterns, including chromosomal dominant inheritance, autosomal recessive inheritance, and X-linked inheritance. Through genetic testing and analysis of patients, it is possible to accurately determine whether they carry mutation genes related to optic atrophy, and predict the progression of the disease and potential complications accordingly. This not only provides valuable genetic counseling and fertility planning guidance for patients and their families, but also helps better understand the disease, discover new therapeutic targets, and lay the foundation for developing more precise and effective drugs or gene therapies in the future.
ObjectiveTo report the BEST1 gene mutations and clinical phenotypes in two pedigrees with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB)．MethodsA retrospective clinical study. From November 2019 to March 2021, in the Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University, the BVMD family (4 patients and 6 family members) and the ARB family (2 patients, 2 family members), a total of 6 patients and 8 normal family members were included in the study. Detailed medical history was obtained; best corrected visual acuity, fundus color photography, electrophysiology, optical coherence tomography and fundus autofluorescence examination were performed. The clinical characteristics for all patients in the two families were analyzed. Three milliliter peripheral venous blood of all participants in the family was collected, and the whole genomic DNA was extracted with gene sequencing using next-generation sequencing technology based on targeted capture. Compared with the database to identify the pathogenicity mutation sites, suspected pathogenic mutation sites were selected, then mutations in other members in the family was assayed by Sanger sequencing. ResultsIn family 1, the proband was demonstrated as typical BVMD, other patients were multifocal vitelliform macular dystrophy. The DNA sequencing result showed that all the 4 patients carried heterozygous missense mutations in exon 3 of BEST1 gene: c.240C>G (p.F80L) (M1) and 2 members carried this mutation, but without clinical phenotype. M1 was a likely-pathogenic mutation reported for the first time. In family 2, the proband and the other patient were diagnosed as ARB. The DNA result showed that the 2 patients carried heterozygous missense mutations in exon 5 and exon 2 of BEST1 gene: c.584C>T (p.A195V) (M2)、c.139C>A (p.R47S) (M3), and a heterozygous frameshift mutation in exon 3 of BEST1 gene: c.235dupT (p.S79Ffs*153) (M4). M2 was a pathogenic mutation reported previously. M3 variant was of undetermined significance. M4 was a first reported pathogenic mutation. ConclusionsThe BEST1 gene mutation is the main cause of BVMD and ARB. Different mutation sites have different clinical phenotypes. BVMD and ARB have genetic and clinical heterogeneity.
Objective To examined gene mutations in thymic carcinoma (TC) patients and to explore prognostic correlates and potential targets for therapy. MethodsWe retrospectively included TC patients in Sichuan Cancer Hospital between January 2015 and Febuary 2021.Whole-exome sequencing was performed on tumor tissues from TC patients and their control peripheral blood samples, and the raw data were subjected to bioinformatics analysis and statistical analysis. Results We finally included 24 TC patients with 16 males and 8 females at a median age of 55 (42-74) years. The highest frequency of single nucleotide mutations in this cohort were in the TTN gene (42%), HSPG2 (29%), and OBSCN (29%). Higher frequency of copy number variations occurred in ZNF276 gene (54%, loss), BEND3 (50%, loss), DHODH (50%, loss), and VAC14 (50%, loss). Microsatellite instability (MSI) phenotype was found in 25% of the patients, and the mean tumor mutation burden (TMB) was 9.86. Conclusion This study is the first comprehensive analysis of the mutation profile of thymic carcinoma in China to date. The mutation frequencies of TTN, OBSCN, and ZNF276 genes were high. The biomarker analysis suggests that patients may benefit from immunotherapy and have a long effective survival.
ObjectiveTo investigate the clinical significancy of K-ras gene mutation in peripheral blood free DNA in patients with non-small cell lung cancer (NSCLC).
MethodsA total of 242 patients pathologically diagnosed with NSCLC in the Third People's Hospital of Chengdu were recruited between January 2013 and August 2015. Both tumor tissues and peripheral blood free DNA were collected for detection of K-ras gene mutation by mutant-enriched liquidchip technology. The detection rate was compared between these two kinds of samples.
ResultsIn tumor tissues, the K-ras gene mutation was detected in 12 cases with a positive rate of 4.96%. While in peripheral blood samples, the K-ras gene mutation was detected in 10 cases with a positive rate of 4.13%. The detection yield of K-ras gene mutation in peripheral blood had a good consistency with that of lung cancer tissues (Kappa value=0.81).
ConclusionK-ras in peripheral blood plasma free DNA can be a surrogate marker for tumor tissues' K-ras gene mutation in screening patients with NSCLC.
ObjectiveTo identify the causative genes of the posterior microphthalmia-retinal pigment degeneration family. MethodsA retrospective clinical study. One child (proband) and 3 family members of a family with posterior microphthalmia-retinitis pigmentosa diagnosed by clinical and genetic examination at Henan Provincial People's Hospital in July 2019 were included in the study. Medical history and family history, and draw pedigree of the patients was collected. Visual acuity, visual field, fundus color photography, optical coherence tomography and electroretinogram (ERG) were examined. The peripheral venous blood of the proband, his parents and sister, and extract the whole genome DNA was collected. Whole-exome sequencing was used to detect genetic variations, the suspected pathogenic variations were verified by Sanger sequencing, and the pathogenicity was determined by bioinformatics analysis. ResultsThe parents discovered the proband was poor vision at the age of 10 months. At the age of 3, the best corrected visual acuity of the right eye and the left eye were 0.3 and 0.4, respectively. No abnormality was found in anterior segment. Extremely high hyperopia in both eyes. The axial length was 14.47 mm and 15.78 mm, respectively. The optic disc of both eyes was relatively small and flushed, retinal folds can be observed in macular area, and no obvious pigment deposition was found. ERG examination showed that the rod system response and the maximal combined response of both eyes decreased slightly to moderately, and the single-flash cone response and the 30 Hz flicker response decreased moderately to severely. Genetic analysis revealed two novel mutations in the membrane frizzled-related protein (MFRP) gene in the proband: c.363delC/p.Thr121Thrfs*16, c.1627C＞T/p .Gln543Stop,37 in exon 4 and 13, the former was a frameshift mutation, encoding 16 amino acids and then terminated, and the latter was an nonsense mutation, truncated 37 amino acids, both which were predicted to be pathogenic and segregate with disease. The mother and sister carried c.363delC, and the father carried c.1627C＞T. ConclusionMFRP gene c.363delC/p.Thr121Thrfs*16, c.1627C＞T/p.Gln543Stop, 37 compound heterozygous mutation may be the pathogenic gene of this family.
ObjectiveTo study the expressions of BRAF gene in papillary thyroid microcarcinoma (PTMC) and papillary thyroid carcinoma (PTC) >1 cm in diameter, and the invasiveness of PTMC and PTC.
MethodsThe data of 275 patients with PTC received surgical treatment and with BRAF gene mutation results in West China Hospital of Sichuan University from 2011 September to 2013 September were retrospectively analyzed. According to the size of tumors, the patients were divided into three groups, was the diameter <1 cm group, 1 cm< diameter≤2 cm group, and diameter >2 cm group,respectively. The ratio of BRAF gene mutation, and the degree of risk of extrathyroidal invasion and lymph node metastasis were compared.
ResultsUnivariate analysis showed that tumor size was not related with the age, gender, and BRAF gene mutation rate (P>0.05), while the tumor size was related with the extrathyroidal invasion and lymph node metastasis (P<0.05), and the ratio of BRAF gene mutation was related with the extrathyroidal invasion and lymph node metastasis (P<0.05). Multivariate analysis showed that tumor size was associated with extrathyroidal extension (P=0.009) and lymph node metastasis (P=0.000).
ConclusionsBRAF gene mutation can increase the extrathyroidal invasion and lymph node metastasis risk of PTC, and it is no significantly correlated with tumor size of PTC. The invasiveness of PTC increases with the increased of tumor size, but the PTMC of BRAF gene mutation positive is still require positive treatment.
ObjectiveTo investigate association between BRAFV600E gene mutation and extrathyroidal extension (ETE) among patients with papillary thyroid carcinoma (PTC).MethodsA retrospective study was conducted to collect all PTC surgical patients in the Renmin Hospital of Wuhan University from 2017 to 2019. The patients tested for BRAFV600E gene mutation were selected, and the association between BRAFV600E gene mutation and ETE were analyzed.ResultsThe BRAFV600E gene mutation test was performed only in 273 cases, 223 and 50 of whom were BRAFV600E gene with and without mutation, respectively; 194 and 79 of whom had ETE and no ETE, respectively. Univariate analysis showed that the incidence rate with BRAFV600E gene mutation was higher in the patients with ETE as compared with the patients without ETE (86.1% vs 70.9%, P=0.003) and the incidence rate of ETE was higher in the patients with BRAFV600E gene mutaton than in the patients without BRAFV600E gene mutaton (74.9% vs 54.0%, P=0.003). In addition, the incidence rates of ETE in the patients with tumor diameter >1 cm, bilaterality, and multifocality were higher than those in the patients with tumor diameter ≤1 cm (86.7% vs 61.3%, P<0.001), unilaterality (89.6% vs 63.8%, P<0.001), and single lesion (85.7% vs 60.9%, P<0.001), respectively. The incidence rate of ETE was increased with the increase of lymph node stage (P=0.003). Multivariate logistic regression analysis showed tumor size >1 cm [OR=3.606, 95%CI (1.758, 7.396), P<0.001], multifocality [OR=2.524, 95%CI (1.154, 5.519), P=0.020], with BRAFV600E gene mutaton [OR=3.022, 95%CI (1.443, 6.326), P=0.003] were the risk factors for ETE.ConclusionThe preliminary results of this study suggest that PTC patients with BRAFV600E gene mutaton are more likely to gross ETE.
Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.
