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Journal of the... 2020The correlation of the angiotensin-converting enzyme () insertion/deletion (I/D) polymorphism with pediatric asthma risk was assessed in this meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The correlation of the angiotensin-converting enzyme () insertion/deletion (I/D) polymorphism with pediatric asthma risk was assessed in this meta-analysis.
METHODS
PubMed, Web of Science, Embase and CNKI databases were systematically searched for relevant literature, followed by application of odds ratios (OR) along with 95% confidence interval (CI) for determining the strength of relationship.
RESULTS
Seven articles with 802 cases and 632 controls fulfilled the inclusion criteria. As a result, the I/D polymorphism was related to elevated pediatric asthma risk (D vs I: OR = 1.87, 95% CI = 1.59-2.20; dominant model: OR =1.53, 95% CI = 1.28-1.81; recessive model: OR =1.54, 95% CI = 1.28-1.85; DD vs II: OR =2.95, 95% CI = 2.19-3.98; DI vs II: OR = 0.96, 95% CI = 0.78-1.19). Subgroup analysis stratified by race revealed significant interrelation in Asians.
CONCLUSION
This meta-analysis demonstrated that the I/D polymorphism might be related to the risk of pediatric asthma.
Topics: Asthma; Child; Gene Deletion; Genetic Predisposition to Disease; Humans; Mutagenesis, Insertional; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Risk Assessment
PubMed: 32475208
DOI: 10.1177/1470320320923475 -
BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
Pediatric Cardiology Aug 2019Tetralogy of Fallot (ToF) is one of the most common cyanotic congenital heart defects. We sought to summarize all available data regarding the epidemiology and... (Meta-Analysis)
Meta-Analysis
Tetralogy of Fallot (ToF) is one of the most common cyanotic congenital heart defects. We sought to summarize all available data regarding the epidemiology and perioperative outcomes of syndromic ToF patients. A PRISMA-compliant systematic literature review of PubMed and Cochrane Library was performed. Twelve original studies were included. The incidence of syndromic ToF was 15.3% (n = 549/3597). The most prevalent genetic syndromes were 22q11.2 deletion (47.8%; 95% CI 43.4-52.2) and trisomy 21 (41.9%; 95% CI 37.7-46.3). Complete surgical repair was performed in 75.2% of the patients (n = 161/214; 95% CI 69.0-80.1) and staged repair in 24.8% (n = 53/214; 95 CI 19.4-30.9). Relief of RVOT obstruction was performed with transannular patch in 64.7% (n = 79/122; 95% CI 55.9-72.7) of the patients, pulmonary valve-sparing technique in 17.2% (n = 21/122; 95% CI 11.5-24.9), and RV-PA conduit in 18.0% (n = 22/122; 95% CI 12.1-25.9). Pleural effusions were the most common postoperative complications (n = 28/549; 5.1%; 95% CI 3.5-7.3). Reoperations were performed in 4.4% (n = 24/549; 95% CI 2.9-6.4) of the patients. All-cause mortality rate was 9.8% (n = 51/521; 95% CI 7.5-12.7). Genetic syndromes are seen in approximately 15% of ToF patients. Long-term survival exceeds 90%, suggesting that surgical management should be dictated by anatomy regardless of genetics.
Topics: Cardiac Surgical Procedures; DiGeorge Syndrome; Down Syndrome; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Postoperative Complications; Pulmonary Valve; Reoperation; Retrospective Studies; Tetralogy of Fallot; Treatment Outcome
PubMed: 31214731
DOI: 10.1007/s00246-019-02133-z -
Journal of Clinical Medicine Feb 2024Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result...
Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.
Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the gene (c.77delT) and a likely pathogenic missense variant in the gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads ( = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases ( = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.
PubMed: 38398243
DOI: 10.3390/jcm13040929 -
BMC Medical Genomics Dec 2022The incidence of hereditary spherocytosis (HS) is approximately 1:2000 in the western population, while it is much lower in the Chinese population. It is difficult to...
BACKGROUND
The incidence of hereditary spherocytosis (HS) is approximately 1:2000 in the western population, while it is much lower in the Chinese population. It is difficult to make a definite diagnosis due to the variable genotypic features and the lack of well-documented evidence for HS patients. Gene sequence examination is helpful for clear diagnosis.
CASE PRESENTATION
We presented the case of a 29-year-old male HS patient with skin yellowness, anorexia, and cholecystolithiasis as the first manifestations. Laboratory examination of the patient and his parents showed a mild reduction in hemoglobin and mean corpuscular hemoglobin concentration, increased reticulocytes, and promotion of indirect bilirubin in the patient and his father. Furthermore, small globular red blood cells with increased osmotic fragility were observed. In particular, the eosin-5'-maleimide binding test provided the strong evidence that band 3 protein was deleted in the erythrocyte membrane. Next-generation sequencing (NGS) and Sanger sequencing further demonstrated a heterozygous nonsense variant (exon16, c.G1985A: p.W662X) in SLC4A1, inherited from his father. Thus, the patient was diagnosed with HS, and then was effectively treated. After splenectomy, the anemia was relieved without any obvious unpleasant side effects.
CONCLUSION
We report an extremely rare case of HS in China that presented with hereditary hemolytic anemia with band 3 deletion resulting from a novel variant of SLC4A1, and systematically review a large number of related literatures. This study, therefore, significantly contributes to the literature on HS.
Topics: Adult; Humans; Male; Anion Exchange Protein 1, Erythrocyte; Asian People; Erythrocytes; Genotype; Heterozygote; Spherocytosis, Hereditary
PubMed: 36463227
DOI: 10.1186/s12920-022-01399-2 -
International Journal of Molecular... Nov 2021Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the DNA sequence. Prostate cancer (PC)...
Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the DNA sequence. Prostate cancer (PC) displays a complex genetic and epigenetic regulation of cell-growth pathways and tumor progression. We performed a systematic literature review (following PRISMA guidelines) focused on the epigenetic regulation of PD-L1 expression in PC. In PC cell lines, CpG island methylation of the promoter negatively regulated PD-L1 expression. Histone modifiers also influence the PD-L1 transcription rate: the deletion or silencing of the histone modifiers MLL3/MML1 can positively regulate PD-L1 expression. Epigenetic drugs (EDs) may be promising in reprogramming tumor cells, reversing epigenetic modifications, and cancer immune evasion. EDs promoting a chromatin-inactive transcriptional state (such as bromodomain or p300/CBP inhibitors) downregulated PD-L1, while EDs favoring a chromatin-active state (i.e., histone deacetylase inhibitors) increased PD-L1 expression. miRNAs can regulate PD-L1 at a post-transcriptional level. miR-195/miR-16 were negatively associated with PD-L1 expression and positively correlated to longer biochemical recurrence-free survival; they also enhanced the radiotherapy efficacy in PC cell lines. miR-197 and miR-200a-c positively correlated to PD-L1 mRNA levels and inversely correlated to the methylation of PD-L1 promoter in a large series. miR-570, miR-34a and miR-513 may also be involved in epigenetic regulation.
Topics: Animals; B7-H1 Antigen; Cell Line, Tumor; CpG Islands; DNA Methylation; Epigenesis, Genetic; Gene Expression; Gene Expression Regulation, Neoplastic; Histone Code; Histones; Humans; Male; MicroRNAs; Promoter Regions, Genetic; Prostatic Neoplasms
PubMed: 34830196
DOI: 10.3390/ijms222212314 -
Translational Cancer Research May 2020Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) exhibit a beneficial therapeutic effect on non-small cell lung cancer (NSCLC). However, almost...
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) exhibit a beneficial therapeutic effect on non-small cell lung cancer (NSCLC). However, almost all patients with EGFR-mutant lung cancer develop drug resistance to these agents. Common drug resistance mechanisms include the mutation, amplification, mutation, polymorphism deletion and gene mutations. Some NSCLC exhibit transformation into small cell lung cancer (SCLC). A patient case of a 56-year-old man with lung adenocarcinoma (with symptoms of a cough and expectoration that had lasted 1 month) who exhibited an mutation (19-Del) and was treated with EGFR-TKIs is reported, which transformed into SCLC after failed to targeted therapy. Pathological examination and genome sequencing were carried out when every time the disease progressed, we obtained more comprehensive information and could keep track of the patient's progress. So, we could adjust the treatment plan at any time according to the results of pathological examination and gene detection. We can get some implications: (I) patients with mutant lung adenocarcinoma with the double inactivation of RB1 and TP53 genes exhibit an increased risk of SCLC transformation; (II) after SCLC transformation, therapeutic strategies should be adequately adjusted, when SCLC was controlled by chemotherapy the targeted therapy should be considered for the treatment of adenocarcinoma; (III) evidence of the benefits of immunotherapy in patients with SCLC transformation is insufficient; (IV) the achievement of the SCLC phenotype is a late phenomenon during TKI therapy and the prognosis of patients after SCLC diagnosis is poor.
PubMed: 35117735
DOI: 10.21037/tcr-19-2291