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Journal of Translational Medicine Jul 2012The 235delC mutation of GJB2 gene is considered as a risk factor for the non-syndromic hearing loss (NSHL), and a significant difference in the frequency and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 235delC mutation of GJB2 gene is considered as a risk factor for the non-syndromic hearing loss (NSHL), and a significant difference in the frequency and distribution of the 235delC mutation has been described world widely.
METHODS
A systematic review was performed by means of a meta-analysis to evaluate the influence of the 235delC mutation on the risk of NSHL. A literature search in electronic databases using keywords "235delC", "GJB2" associated with "carrier frequency" was conducted to include all papers from January 1999 to June 2011. A total of 36 papers were included and there contained 13217 cases and 6521 controls derived from Oceania, American, Europe and Asian.
RESULTS
A remarkable heterogeneity between these studies was observed. The combined results of meta-analysis showed that the 235delC mutant increased the risk of NSHL (OR = 7.9, 95%CI 4.77 ~ 13.11, P <0.00001). Meanwhile, heterogeneity of genetic effect was also observed due to the ethnic specificity and regional disparity. Therefore, the stratified meta-analysis was subsequently conducted and the results indicated that the 235delC mutation was significantly correlated with the risk of NHSL in the East Asian and South-east Asian populations (OR = 12.05, 95%CI 8.33~17.44, P <0.00001), but not significantly in the Oceania and European populations (OR = 10.36, 95%CI: 4.68~22.96, Z = 1.68, P >0.05).
CONCLUSIONS
The 235delC mutation of GJB2 gene increased the risk of NHSL in the East Asian and South-east Asian populations, but non-significantly associated with the NSHL susceptibility in Oceania and European populations, suggesting a significant ethnic specificity of this NSHL-associated mutation.
Topics: Asia; Connexin 26; Connexins; Gene Deletion; Genetic Carrier Screening; Hearing Loss; Humans; Mutation
PubMed: 22747691
DOI: 10.1186/1479-5876-10-136 -
Jornal de Pediatria 2015This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential... (Review)
Review
OBJECTIVES
This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential association with pediatric stroke and cerebral palsy (CP).
SOURCES
Scientific articles published from 1993 to 2013, written in Portuguese, English, French, and Spanish, were selected and reviewed. The publications were searched in electronic databases, and also in the collections of local libraries. The terms "hereditary thrombophilia", "polymorphisms", "mutation", "pediatric strokes", and "cerebral palsy" were used for the research.
SUMMARY OF THE FINDINGS
The search in databases and in the bibliographic references retrieved 75 articles for inclusion in this review. Studies that investigated hereditary thrombophilias and their associations to CP and arterial and venous pediatric stroke presented contradictory results. The meta-analysis and case-control studies that showed positive results for this association described only slightly increased relative risks and sometimes had questionable conclusions. The association of two or more hereditary thrombophilias, or the association between thrombophilia and other specific clinical risk factors, suggest a higher risk of CP and pediatric stroke than isolated hereditary thrombophilia.
CONCLUSIONS
Larger, multicenter studies should be developed in order to elucidate the role of mutations leading to hereditary thrombophilia and the development of CP and pediatric stroke. The complex and multifactorial etiology of CP and stroke makes this an arduous and difficult task; however, the benefits generated by these studies are immeasurable.
Topics: Case-Control Studies; Cerebral Palsy; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Intracranial Thrombosis; Meta-Analysis as Topic; Mutation; Polymorphism, Genetic; Risk Factors; Stroke; Thrombophilia
PubMed: 25451211
DOI: 10.1016/j.jped.2014.08.004 -
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 -
Allergy and Asthma Proceedings Jan 2021Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor (C1-INH) gene Serpin Family G Member 1(), which results in either the decreased synthesis of...
Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor (C1-INH) gene Serpin Family G Member 1(), which results in either the decreased synthesis of normal C1-INH (C1-INH-HAE type I) or expression of unfunctional C1-INH (C1-INH-HAE type II). In recent studies, emotional stress was reported by patients as the most common trigger factor for C1-INH-HAE attacks. Moreover, patients reported considerable distress over the significant variability and uncertainty with which the disease manifests, in addition to the impact of physical symptoms on their overall quality of life. We did a systematic review of the literature to shed light on the advancements made in the study of how stress and psychological processes impact C1-INH-HAE. All of the articles on C1-INH-HAE were analyzed up to December 2019. Both medical data bases and psychological data bases were examined. The keywords (KWs) used for searching the medical and psychological data bases were the following: "hereditary angioedema," "psychology," "stress," "anxiety," and "depression." Of a total of 2549 articles on C1-INH-HAE, 113 articles were retrieved from the literature search by using the related KWs. Twenty-one of these articles were retrieved, examined, and classified. Although the literature confirmed that stress may induce various physical diseases, it also warned against making simplistic statements about its incidence that did not take into account the complexity and multicausality of factors that contribute to C1-INH-HAE expression.
Topics: Angioedemas, Hereditary; Causality; Complement C1 Inhibitor Protein; Humans; Mutation; Psychological Distress
PubMed: 33404395
DOI: 10.2500/aap.2021.42.200073 -
BMC Cancer Aug 2023Breast cancer susceptibility gene (BRCA) mutation carriers are at an increased risk for breast, ovarian, prostate and pancreatic cancers. However, the role of BRCA is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breast cancer susceptibility gene (BRCA) mutation carriers are at an increased risk for breast, ovarian, prostate and pancreatic cancers. However, the role of BRCA is unclear in colorectal cancer; the results regarding the association between BRCA gene mutations and colorectal cancer risk are inconsistent and even controversial. This study aimed to investigate whether BRCA1 and BRCA2 gene mutations are associated with colorectal cancer risk.
METHODS
In this systematic review, we searched PubMed/MEDLINE, Embase and Cochrane Library databases, adhering to PRISMA guidelines. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Unadjusted odds ratios (ORs) were used to estimate the probability of Breast Cancer Type 1 Susceptibility gene (BRCA1) and Breast Cancer Type 2 Susceptibility gene (BRCA2) mutations in colorectal cancer patients. The associations were evaluated using fixed effect models.
RESULTS
Fourteen studies were included in the systematic review. Twelve studies, including seven case-control and five cohort studies, were included in the meta-analysis. A significant increase in the frequency of BRCA1 and BRCA2 mutations was observed in patients with colorectal cancer [OR = 1.34, 95% confidence interval (CI) = 1.02-1.76, P = 0.04]. In subgroup analysis, colorectal cancer patients had an increased odds of BRCA1 (OR = 1.48, 95% CI = 1.10-2.01, P = 0.01) and BRCA2 (OR = 1.56, 95% CI = 1.06-2.30, P = 0.02) mutations.
CONCLUSIONS
BRCA genes are one of the genes that may increase the risk of developing colorectal cancer. Thus, BRCA genes could be potential candidates that may be included in the colorectal cancer genetic testing panel.
Topics: Male; Humans; Genes, Tumor Suppressor; Genetic Testing; Mutation; Colorectal Neoplasms; Breast Neoplasms
PubMed: 37644384
DOI: 10.1186/s12885-023-11328-w -
Breast (Edinburgh, Scotland) Dec 2021Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type).
MATERIAL AND METHODS
Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation.
RESULTS
Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results.
CONCLUSION
Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve.
Topics: Anti-Mullerian Hormone; Breast Neoplasms; Female; Heterozygote; Humans; Mutation; Ovarian Reserve
PubMed: 34627117
DOI: 10.1016/j.breast.2021.09.006 -
Oncotarget Oct 2016BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on... (Meta-Analysis)
Meta-Analysis Review
BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling. Data from 297, 402 patients with BC were pooled from 34 studies. The median prevalence rates of BRCA1 and BRCA2 mutations were 14.5% and 8.3%, respectively. BRCA mutations were associated with worse OS (BRCA1: HR = 1.69, 95% CI, 1.35 to 2.12, p < 0.001; BRCA2: HR = 1.50, 95% CI 1.03 to 2.19, p = 0.034). However, this did not translate into poor BCSS (BRCA1: HR = 1.14, 95% CI, 0.81 to 1.16, p = 0.448; BRCA2: HR = 1.16; 95% CI 0.82 to 1.66, p = 0.401) or EFS (BRCA1: HR = 1.10, 95% CI, 0.86 to 1.41, p = 0.438; BRCA2: HR= 1.09; 95% CI 0.81 to 1.47, p = 0.558). Several studies analyzed BRCA1 and BRCA2 mutations together and found no impact on OS (HR = 1.21; 95% CI, 0.73 to 2.00, p = 0.454) or EFS (HR = 0.94; 95% CI, 0.60 to 1.48, p = 0.787). BRCA1 and BRCA2 mutations were associated with poor OS in patients with BC, but had no significant impact on BCSS or EFS. An improved survival was observed in BC patients who had BRCA1 mutation and treated with endocrinotherapy. The results may have therapeutic and prognostic implications important for BRCA mutation carriers with BC.
Topics: Adult; Aged; Breast Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Humans; Middle Aged; Mutation; Publication Bias
PubMed: 27659521
DOI: 10.18632/oncotarget.12158 -
World Neurosurgery Mar 2018Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located within the temporal and insular area. The association between IDH1 and IDH2 mutations with preoperative seizures in glioma and the magnitude of this association in low-grade versus high-grade gliomas are unclear. To clarify this relationship, a systematic review and meta-analysis was performed.
METHODS
Following accepted guidelines and systematic review recommendations, electronic searches were performed in journal databases up to May 2017. Data were extracted and pooled via meta-analysis.
RESULTS
We compared 782 patients with IDH1 and IDH2 mutations with 803 patients with wild-type IDH1 and IDH2 before surgery. There was a significant difference in seizure incidence between the IDH1 mutation group (61.6%) and wild-type IDH1 group (32.1%) (odds ratio 2.76; 95% confidence interval, 1.26-6.02; I = 73%; P = 0.01). Similar findings were observed in analysis of IDH1 and IDH2 mutations (odds ratio 2.74; 95% confidence interval, 1.74-4.33; I = 58%; P < 0.0001). The difference remained in both mutation groups (IDH1, IDH1 and IDH2) with grade II gliomas but not with grade III and IV gliomas. Patients with grade II gliomas showed a higher rate of IDH1 and IDH2 mutations and seizures than patients with grade III and IV gliomas.
CONCLUSIONS
This study demonstrated a significant association of IDH1 and IDH2 mutations with incidence of preoperative seizures. This association was significant only in patients with low-grade glioma (grade II) and not in patients with higher grade gliomas (grade III and IV).
Topics: Brain Neoplasms; Gene Frequency; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Seizures
PubMed: 29288860
DOI: 10.1016/j.wneu.2017.12.112 -
Current Pediatric Reviews 2023Silver-Russell syndrome (SRS) is a developmental disorder involving extreme growth failure, characteristic facial features and underlying genetic heterogeneity. As the...
BACKGROUND
Silver-Russell syndrome (SRS) is a developmental disorder involving extreme growth failure, characteristic facial features and underlying genetic heterogeneity. As the clinical heterogeneity of SRS makes diagnosis a challenging task, the worldwide incidence of SRS could vary from 1:30,000 to 1:100,000. Although various chromosomal, genetic, and epigenetic mutations have been linked with SRS, the cause had only been identified in half of the cases.
MATERIAL AND METHODS
To have a better understanding of the SRS clinical presentation and mutation/ epimutation responsible for SRS, a systematic review of the literature was carried out using appropriate keywords in various scientific databases (PROSPERO protocol registration CRD42021273211). Clinical features of SRS have been compiled and presented corresponding to the specific genetic subtype. An attempt has been made to understand the recurrence risk and the role of model organisms in understanding the molecular mechanisms of SRS pathology, treatment, and management strategies of the affected patients through the analysis of selected literature.
RESULTS
156 articles were selected to understand the clinical and molecular heterogeneity of SRS. Information about detailed clinical features was available for 228 patients only, and it was observed that body asymmetry and relative macrocephaly were most prevalent in cases with methylation defects of the 11p15 region. In about 38% of cases, methylation defects in ICRs or genomic mutations at the 11p15 region have been implicated. Maternal uniparental disomy of chromosome 7 (mUPD7) accounts for about 7% of SRS cases, and rarely, uniparental disomy of other autosomes (11, 14, 16, and 20 chromosomes) has been documented. Mutation in half of the cases is yet to be identified. Studies involving mice as experimental animals have been helpful in understanding the underlying molecular mechanism. As the clinical presentation of the syndrome varies a lot, treatment needs to be individualized with multidisciplinary effort.
CONCLUSION
SRS is a clinically and genetically heterogeneous disorder, with most of the cases being implicated with a mutation in the 11p15 region and maternal disomy of chromosome 7. Recurrence risk varies according to the molecular subtype. Studies with mice as a model organism have been useful in understanding the underlying molecular mechanism leading to the characteristic clinical presentation of the syndrome. Management strategies often need to be individualized due to varied clinical presentations.
Topics: Humans; Animals; Mice; Mice, Inbred ICR; Silver-Russell Syndrome; Uniparental Disomy; Genomic Imprinting
PubMed: 35293298
DOI: 10.2174/1573396318666220315142542 -
Orphanet Journal of Rare Diseases Jun 2023CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain... (Review)
Review
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
Topics: Humans; Neuroglia; Leukoencephalopathies; Brain; Mutation; Nervous System Malformations; Atrophy
PubMed: 37349768
DOI: 10.1186/s13023-023-02772-9