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Seizure Mar 2024To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence.
PURPOSE
To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence.
METHODS
Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy.
RESULTS
Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources.
SIGNIFICANCE
Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.
Topics: Humans; Epilepsy; Seizures; Genetic Testing; Mutation; Databases, Factual; Phenotype
PubMed: 37777370
DOI: 10.1016/j.seizure.2023.09.021 -
Surgical Neurology International 2023Lhermitte-Duclos disease (LDD) is a rare tumor, with only about 300 reported cases. It often shows comorbidity with Cowden syndrome (CS); however, it can occur by... (Review)
Review
BACKGROUND
Lhermitte-Duclos disease (LDD) is a rare tumor, with only about 300 reported cases. It often shows comorbidity with Cowden syndrome (CS); however, it can occur by itself. Radiologically, the "tiger-stripe" appearance is considered pathognomonic. Surgical resection remains the mainstay of treatment. This report aims to describe the clinical and radiological characteristics of LDD and its relationship with CS according to age group.
METHODS
PubMed electronic databases were searched in August 2022. The search terms included "Lhermitte- Duclos disease" and "dysplastic gangliocytoma," which yielded 297 and 103 research articles, respectively. The articles were collected and reviewed by three researchers.
RESULTS
Out of 400 identified articles, we analyzed 302 reported cases. The mean age at presentation was 33.6 ± 16 years; 171 patients (56.6%) were female, and 123 (40.7%) were male. The most commonly reported symptom was headache (174 patients, 57.6%), followed by ataxia (109, 36.1%). In addition, 99 cases (32.8%) were associated with CS, and 60 (19.9%) had a confirmed phosphatase and tensin homolog () mutation. A tiger-stripe appearance was observed in 208 cases (58.7%); surgical resection was performed in 64.2% of the cases. Mortality and recurrence rates were 4.3% and 8.6%, respectively. No statistically significant difference was found between adult- and pediatric-onset LDD for the association with CS ( = 0.128).
CONCLUSION
Our findings suggest that adult and pediatric LDD have major commonalities; however, further prospective studies are warranted.
PubMed: 37810307
DOI: 10.25259/SNI_555_2023 -
Neurological Sciences : Official... Sep 2023Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common... (Review)
Review
BACKGROUND AND AIMS
Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%). To date, 44 patients with FDXR mutations have been reported. We describe here on two new patients, siblings, who presented with a quite different phenotype compared to previously described patients.
METHODS
Clinical, neurophysiological, and genetic features of two siblings and a systematic literature review focused on the clinical spectrum of the disease are described.
RESULTS
Both patients presented with an acute-sub-acute onset of peripheral neuropathy and only in later stages of the disease developed the typical features of FDXR-associated disease.
INTERPRETATION
The peculiar clinical presentation at onset and the evolution of the disease in our patients and in some cases revised from the literature shed lights on a new possible phenotype of FDXR-associated disease: a peripheral neuropathy which can mimic an acute inflammatory disease.
Topics: Humans; Ataxia; Cerebellar Ataxia; Diagnosis, Differential; Mutation; Peripheral Nervous System Diseases; Phenotype; Ferredoxin-NADP Reductase
PubMed: 37046037
DOI: 10.1007/s10072-023-06790-0 -
Cancer Treatment Reviews Sep 2023Since their first introduction in clinical practice, immune checkpoint inhibitors showed limited benefit in patients with NSCLC harboring EGFR mutations. With the... (Review)
Review
BACKGROUND
Since their first introduction in clinical practice, immune checkpoint inhibitors showed limited benefit in patients with NSCLC harboring EGFR mutations. With the rationale of increasing immune activation, combinatorial ICI strategies have been evaluated also in this subgroup of patients.
METHODS
We performed a systematic review on efficacy of ICI-based strategies in EGFR-mutant NSCLC according to most updated evidence.
RESULTS
Overall, ICI monotherapy and ICI plus chemotherapy confirm to be ineffective in EGFR-mutant NSCLC, whereas the combination of ICI with antiangiogenic and chemotherapy showed promising results. Limited data are available with alternative ICI combination strategies, driven by strong biological rationale of modulating the tumor immune microenvironment.
CONCLUSIONS
To date, the available evidence do not support the use of ICI in patients with NSCLC harboring EGFR mutations. Clinical trials are ongoing to define which is the best timing and exploring novel combinations with ICI in this specific disease.
PubMed: 37481836
DOI: 10.1016/j.ctrv.2023.102602 -
Journal of Epidemiology Dec 2023The possible association between cigarette smoking and breast cancer risk has been quite controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The possible association between cigarette smoking and breast cancer risk has been quite controversial.
METHODS
We conducted a systematic review and meta-analysis of all available observational studies published on the issue up to January 2020. Random-effects models were used to compute pooled relative risks (RRs) for cigarette smoking status and dose-risk relationships were evaluated using one-stage random-effects dose-response models.
RESULTS
A total of 169 studies were selected, providing a pooled RR for breast cancer of 1.07 (95% confidence interval [CI], 1.05-1.10) for current, 1.08 (95% CI, 1.06-1.10) for former, and 1.09 (95% CI, 1.07-1.11) for ever smokers, compared to never smokers. Results were consistent in case-control and cohort studies. No meaningful differences were observed across strata of most covariates considered, nor according to relevant genetic mutations and polymorphisms (ie, BRCA mutation, N-acetyltransferase and glutathione S-transferase genotypes, and P53). Breast cancer risk increased linearly with intensity of smoking (RR 1.12; 95% CI, 1.08-1.16 for 20 cigarettes/day and 1.26; 95% CI, 1.17-1.36 for 40 cigarettes/day), and with increasing duration of smoking (RR 1.05; 95% CI, 1.03-1.08 for 20 years of smoking and 1.11; 95% CI, 1.06-1.16 for 40 years of smoking).
CONCLUSION
The present large and comprehensive meta-analysis-conducted using an innovative approach for study search-supports the evidence of a causal role of tobacco smoking on breast cancer risk.
Topics: Humans; Female; Risk Factors; Cigarette Smoking; Breast Neoplasms; Japan; Cohort Studies
PubMed: 36967121
DOI: 10.2188/jea.JE20220206 -
Journal of Cancer Research and Clinical... Nov 2023The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected... (Review)
Review
PURPOSE
The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome.
METHODS
Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant.
RESULTS
We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021).
CONCLUSIONS
Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.
Topics: Humans; Male; Female; Infant; Stomach Neoplasms; Pedigree; Genetic Testing; Adenocarcinoma; Germ Cells; Cadherins; Germ-Line Mutation; Genetic Predisposition to Disease; Antigens, CD
PubMed: 37639007
DOI: 10.1007/s00432-023-05318-5 -
Journal of Assisted Reproduction and... Oct 2023To establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy... (Meta-Analysis)
Meta-Analysis
PURPOSE
To establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy rate per embryo transfer compared to conventional morphological assessment.
METHODS
A systematic literature search was conducted using PubMed, EMBASE and Cochrane database from 1st March 2000 until 1st March 2022. Studies comparing reproductive outcomes following in vitro fertilisation using comprehensive chromosome screening (CCS) at the blastocyst stage with traditional morphological methods were evaluated.
RESULTS
Of the 1307 citations identified, six randomised control trials (RCTs) and ten cohort studies fulfilled the inclusion criteria. The pooled data identified a benefit between PGT-A and control groups in the composite outcome of live birth rate and ongoing pregnancy per embryo transfer in both the RCT (RR 1.09, 95% CI 1.02-1.16) and cohort studies (RR 1.50, 95% CI 1.28-1.76). Euploid embryos identified by CCS were more likely to be successfully implanted amongst the RCT (RR 1.20, 95% CI 1.10-1.31) and cohort (RR 1.69, 95% CI 1.29-2.21) studies. The rate of miscarriage per clinical pregnancy is also significantly lower when CCS is implemented (RCT: RR 0.73, 95% CI 0.56-0.96 and cohort: RR 0.48, 95% CI 0.32-0.72).
CONCLUSIONS
CCS-based PGT-A at the blastocyst biopsy stage increases the composite outcome of live births and ongoing pregnancies per embryo transfer and reduces the rate of miscarriage compared to morphological assessment alone. In view of the limited number of studies included and the variation in methodology between studies, future reviews and analyses are required to confirm these findings.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Aneuploidy; Birth Rate; Blastocyst; Genetic Testing
PubMed: 37479946
DOI: 10.1007/s10815-023-02866-0 -
Head & Neck Sep 2023In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science,... (Review)
Review
In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched to access cases of SPA in salivary glands. One hundred and thirty cases of SPA were found across 61 selected articles. SPA affected mainly the parotid gland of adults with a mean age of 44.6 years old, with a slight preference for females. The lesion was usually presented as a painless firm mass with a long period of evolution. Histologically, they are well-delimitated lesions composed of acinar and ductal elements with a variety of cytomorphologic features surrounded by a densely collagenized stroma. PI3K was the most common gene mutation related to SPA. SPA is a benign condition that mainly affects the parotid gland of female patients and it is usually treated by surgical resection with a good prognosis.
Topics: Adult; Humans; Female; Parotid Gland; Adenoma; Sclerosis
PubMed: 37403748
DOI: 10.1002/hed.27435 -
Pediatric Neurology Aug 2023Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in ATP7B. R778L is the most common ATP7B mutation in China.
METHODS
To estimate whether R778L is associated with the onset age of WD and other clinical variables. Genotyping results of ATP7B gene were collected in our 22 patients with WD. We then conducted a systematic review and meta-analysis in databases, using the keywords Wilson disease and R778L mutation.
RESULTS
After the screening, a total of 23 studies were included, including 3007 patients with WD. Patients with R778L mutation presented at an earlier age (standardized mean difference [SMD] = -0.18 [95% confidence interval, -0.28 to 0.08], P = 0.0004) and had lower ceruloplasmin concentration (SMD = -0.21 [95% confidence interval, -0.40 to -0.02], P = 0.03) than the patients without the R778L mutation. However, sex (odds ratio [OR] = 1.07 [95% confidence interval, 0.89 to 1.29], P = 0.32) and first presentation were not associated with R778L mutation in WD (hepatic: OR = 1.37 [95% confidence interval, 0.87 to 2.16, P = 0.17; neurological: OR = 0.79 [95% confidence interval, 0.48 to 1.30, P = 0.35; mix: OR = 1.04 [95% confidence interval, 0.42 to 2.53, P = 0.87; asymptomatic/others: OR = 1.98 [95% confidence interval, 0.49 to 7.96, P = 0.34).
CONCLUSIONS
Our results indicated that the R778L mutation is associated with an earlier presentation and lower ceruloplasmin concentration in China.
Topics: Humans; Ceruloplasmin; China; Copper-Transporting ATPases; Hepatolenticular Degeneration; Mutation
PubMed: 37354629
DOI: 10.1016/j.pediatrneurol.2023.04.026 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z