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Orphanet Journal of Rare Diseases Jul 2022Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic... (Review)
Review
BACKGROUND
Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures.
METHODS
We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing.
RESULTS
A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced.
CONCLUSIONS
Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD.
TRIAL REGISTRY
PROSPERO; No.: CRD42021257804; URL: www.crd.york.ac.uk/prospero/.
Topics: Cilia; Ciliary Motility Disorders; Delayed Diagnosis; Genotype; Humans; Kartagener Syndrome; Mutation; Phenotype
PubMed: 35854386
DOI: 10.1186/s13023-022-02427-1 -
European Journal of Cancer (Oxford,... Sep 2021There are limited data comparing the OncotypeDX© Recurrence Score (RS) among BRCA mutation carriers and patients with sporadic breast cancer. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There are limited data comparing the OncotypeDX© Recurrence Score (RS) among BRCA mutation carriers and patients with sporadic breast cancer.
AIM
To compare RS results among BRCA mutation carriers and patients with sporadic breast cancer in oestrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer.
METHODS
A systematic review was performed in accordance with PRISMA and MOOSE guidelines. Retrospective cohort studies comparing RS in BRCA mutation carriers and cases of sporadic cancer were included. Dichotomous variables were pooled as odds ratios (ORs) and associated 95% confidence intervals (CIs) using the Mantel-Haenszel method.
RESULTS
Five studies involving 4286 patients were included with a mean age of 60 years (range 22-85). Overall, 7.8% were BRCA mutation carriers (333/4286). The mean RS was 18.0 (range 0-71), and the mean RS in BRCA carriers was 25 (range 10-71) versus 18.4 in cases of sporadic disease (range 0-62). Patients with sporadic cancers were more likely to have RS < 18 (OR 0.27, 95% CI 0.14-0.51, P = 0.010). BRCA mutation carriers were more likely to have RS 18-30 (OR 1.74, 95% CI 1.28-2.37, P < 0.001) and RS > 30 (OR 3.71, 95% CI 2.55-5.40, P < 0.001).
CONCLUSION
There is an increased likelihood of high-risk RS among patients with known germline BRCA mutations when compared to patients developing sporadic ER+/HER2-early breast cancer. This study offers insight into genomic testing results within BRCA mutation carriers which may be useful in counselling patients with BRCA mutations in future practice.
Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Heterozygote; Humans; Middle Aged; Mutation; Receptor, ErbB-2; Receptors, Estrogen; Young Adult
PubMed: 34284256
DOI: 10.1016/j.ejca.2021.06.032 -
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 -
Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis.Viruses Mar 2023Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive... (Meta-Analysis)
Meta-Analysis Review
Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.
Topics: Humans; Spike Glycoprotein, Coronavirus; COVID-19; SARS-CoV-2; Mutation; Protein Binding
PubMed: 37112836
DOI: 10.3390/v15040856 -
Prenatal Diagnosis Feb 2023The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies.
METHODS
A systematic review and meta-analysis was performed to assess cfDNA accuracy for prenatal detection of 45,X, 47,XXY, 47,XXX and 47,XYY. Inclusion was restricted to studies published between January 2010 and December 2021 reporting both cfDNA and confirmatory diagnostic test results.
RESULTS
For 45,X, the sensitivity was 98.8% (95%CI 94.6%-100%), specificity 99.4% (95%CI 98.7%-99.9%) and positive predictive value (PPV) 14.5% (95%CI 7.0%-43.8%). For 47,XXY, the sensitivity was 100% (95%CI 99.6%-100%), specificity 100% (95%CI 99.9%-100%) and PPV 97.7% (95%CI 78.6%-100%). For 47,XXX, the sensitivity was 100% (95%CI 96.9%-100%), specificity 99.9% (95%CI 99.7%-100%) and PPV 61.6% (95%CI 37.6%-95.4%). For 47,XYY, the sensitivity was 100% (95%CI 91.3%-100%), specificity 100% (95% CI 100%-100%) and PPV 100% (95%CI 76.5%-100%). All four SCAs had estimated negative predictive values (NPV) exceeding 99.99%, though false negatives were reported.
CONCLUSIONS
This analysis suggests that cfDNA is a reliable screening test for SCA, though both false negatives and false positives were reported. These estimates of test performance are derived from pregnancies at high pretest risk for aneuploidy, limiting the generalisability to average risk pregnancies.
Topics: Pregnancy; Female; Humans; Cell-Free Nucleic Acids; Sex Chromosome Aberrations; Aneuploidy; Chromosomes, Human, X; Prenatal Diagnosis
PubMed: 36588186
DOI: 10.1002/pd.6298 -
International Immunopharmacology Nov 2023Tumor mutation burden (TMB) is a complement to traditional biomarkers related to the efficacy of immune checkpoint inhibitors (ICIs). The relationship between TMB and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tumor mutation burden (TMB) is a complement to traditional biomarkers related to the efficacy of immune checkpoint inhibitors (ICIs). The relationship between TMB and the efficacy of ICIs in gastric cancer was controversial. The systematic review and meta-analysis were conducted to investigate the predictive value of TMB on survival of gastric cancer patients treated with ICIs.
METHODS
We searched the databases PubMed, Embase, and Web of Science for articles, then screened eligible articles according to inclusion criteria. The effective data were extracted to calculate the pooled effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS), then perform publication bias, sensitivity analysis, and subgroup analysis by STATA 16.0.
RESULTS
The high TMB patients showed significantly longer survival than the low TMB patients (OS: HR 0.65,95% CI 0.55, 0.77, p < 0.001; PFS: HR 0.51, 95% CI 0.33, 0.77, p = 0.001). In the Asian subgroup, patients with high TMB exhibited better prognosis compared to low TMB (OS: HR 0.56, 95% CI 0.43, 0.72, p < 0.001; PFS: HR 0.45, 95% CI 0.28, 0.72, p = 0.001). In the non-Asian subgroup, the survival benefit was observed to be skewed toward patients with high TMB, but it was not statistically significant (OS:HR 0.61, 95% CI 0.32, 1.16, p = 0.133; PFS:HR 0.68, 95% CI 0.31, 1.48, p = 0.322).
CONCLUSIONS
This meta-analysis demonstrated that gastric cancer patients with high TMB showed significant benefits from ICIs compared to those with low TMB patients, particularly in Asian populations.
Topics: Humans; Immune Checkpoint Inhibitors; Stomach Neoplasms; Databases, Factual; Progression-Free Survival; Mutation
PubMed: 37748223
DOI: 10.1016/j.intimp.2023.110986 -
International Journal of Molecular... Nov 2023Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample... (Meta-Analysis)
Meta-Analysis Review
Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample should be examined in assessing drug targets. This study systematically analyzed all the literature on primary melanoma and its matched metastasis. Following PRISMA guidelines, we searched multiple medical databases for relevant publications from January 2000 to December 2022, assessed the quality of the primary-level studies using the QUIPS tool, and summarized the concordance rate of the most reported genes using the random-effects model. Finally, we evaluated the inter-study heterogeneity using the subgroup analysis. Thirty-one studies investigated the concordance of and in 1220 and 629 patients, respectively. The pooled concordance rate was 89.4% [95% CI: 84.5; 93.5] for and 97.8% [95% CI: 95.8; 99.4] for . When high-quality studies were considered, only mutation status consistency increased. Five studies reported the concordance status of c (93%, 44 patients) and promoter (64%, 53 patients). Lastly, three studies analyzed the concordance of cancer genes involved in the signaling pathways, apoptosis, and proliferation, such as (25%, four patients), (44%, nine patients), and (20%, five patients). Our study found that the concordance of known drug targets (mainly ) during melanoma progression is higher than in previous meta-analyses, likely due to advances in molecular techniques. Furthermore, significant heterogeneity exists in the genes involved in the melanoma genetic makeup; although our results are based on small patient samples, more research is necessary for validation.
Topics: Humans; Melanoma; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Mutation; Melanoma, Cutaneous Malignant
PubMed: 38003476
DOI: 10.3390/ijms242216281 -
BMC Genomic Data Jan 2024In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence. (Meta-Analysis)
Meta-Analysis
PURPOSE
In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence.
MATERIAL AND METHOD
We systematically searched three databases including PubMed, Scopus, and Google Scholar up to August 2023; and reviewed 23 cohorts and cross-sectional studies to explore the association between BRCA1/2 mutations and uterine cancer incidence.
RESULTS
This systematic review comprised a total of 21 cohort studies and 2 cross-sectional studies after the screening process. According to meta-analysis the prevalence of the BRCA1/2 gene in patients with uterine cancer was 0.02 (95%CI = [0.01,0.03], P < 0.01, I = 94.82%) CONCLUSIONS: Our meta-analysis investigates a 2% prevalence of BRCA1/2 mutation in patients with uterine cancer. Patients with BRCA1/2 mutations might be more conscious of uterine malignancies.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Cross-Sectional Studies; Mutation; Uterine Neoplasms
PubMed: 38297203
DOI: 10.1186/s12863-024-01189-y -
European Journal of Medical Research Feb 2022To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on...
OBJECTIVE
To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on susceptibility to corona virus disease 2019 (COVID-19) and patient prognosis.
INTRODUCTION
From December 2019 to the current time, an outbreak of epidemic of COVID-19, characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred around the world. It is now clear that SARS-CoV-2 binds to human ACE2 receptors, with expression of these receptors correlated with the rate of SARS-CoV-2 infection and mortality. Polymorphisms in individual patient factors, such as ACE2 and TMPRSS2 genes have been linked with an increase in negative outcomes, although evidence to affirm remains debatable.
METHODS
Here, we performed a systematic review, based on guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, with the aim of assessing whether polymorphisms in ACE2 and TMPRSS2 genes affect the COVID-19 condition. We extensively searched PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science databases, for relevant articles and reports published in English between December 2019 and December 2021.
RESULTS
A total of 495 full-text articles were downloaded, of which 185 were excluded after preliminary examination as they were duplicates. Finally, 310 articles were evaluated, by reading their titles and abstracts, and 208 of them eliminated based on our selection criteria. Finally, 33 articles met our inclusion criteria and were included in the final assessment. Genetic data from 33,923 patients with COVID-19 drawn from the general population and deriving from over 160 regions and 50 countries, as well as approximately 560,000 samples from global-public genetic databases, were included in our analysis. Ultimately, we identified 10 SNPs and 21 mutations in the ACE2 gene, along with 13 SNPs and 12 variants in the TMPRSS2 gene, which may be associated with COVID-19.
CONCLUSIONS
ACE2 and TMPRSS2 play vital roles in the onset, development, and prognosis of SARS-CoV-2 infection, and have both been strongly associated with vulnerability, intensity, and the clinical result of COVID-19. Overall, these genetic factors may have potential for future development of personalized drugs and vaccines against COVID-19.
TRIAL REGISTRATION
CRD42021239400 in PROSPERO 2021.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genetic Predisposition to Disease; Humans; Mutation; Polymorphism, Single Nucleotide; SARS-CoV-2; Serine Endopeptidases
PubMed: 35193695
DOI: 10.1186/s40001-022-00647-6 -
The Journal of International Medical... Jan 2022Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the / genes are often observed in BC cases and largely increase the lifetime risk...
OBJECTIVE
Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the / genes are often observed in BC cases and largely increase the lifetime risk of having BC. Because of the paucity of high-quality data on the molecular spectrum of mutations in South Asian populations, we aimed to explore these mutations among South Asian countries.
METHODS
A systematic literature search was performed for the and gene mutation spectrum using electronic databases such as PubMed, EMBASE, and Google Scholar. Twenty studies were selected based on specific inclusion and exclusion criteria.
RESULTS
The 185delAG (c.68_69del) mutation in exon 2 of was the most common recurrent mutation and founder mutation found. Various intronic variants, variants of unknown significance, large genomic rearrangements, and polymorphisms were also described in some studies.
CONCLUSIONS
The South Asian population has a wide variety of genetic mutations of and that differ according to countries and ethnicities. A stronger knowledge of various population-specific mutations in these cancer susceptibility genes can help provide efficient strategies for genetic testing.
Topics: Asia; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Female; Genes, BRCA2; Genetic Predisposition to Disease; Humans; Mutation; Neoplasm Recurrence, Local; Ovarian Neoplasms; Spectrum Analysis
PubMed: 35000471
DOI: 10.1177/03000605211070757