-
Clinical Genetics Sep 2023Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process.... (Meta-Analysis)
Meta-Analysis Review
Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process. Here we aimed to find the failure pattern of tooth eruption among five genetic diseases. Both systematic review and meta-analysis were used to identify the genotype-phenotype associations of unerupted teeth. The meta-analysis was based on the characteristics of abnormal tooth eruption in 223 patients with the mutations in PTH1R, RUNX2, COL1A1/2, CLCN7, and FAM20A respectively. We found all the patients presented selective failure of tooth eruption (SFTE). Primary failure of eruption patients with PTH1R mutations showed primary or isolated SFTE1 in the first and second molars (59.3% and 52% respectively). RUNX2 related cleidocranial dysplasia usually had SFTE2 in canines and premolars, while COL1A1/2 related osteogenesis imperfecta mostly caused SFTE3 in the maxillary second molars (22.9%). In CLCN7 related osteopetrosis, the second molars and mandibular first molars were the most affected. While FAM20A related enamel renal syndrome most caused SFTE5 in the second molars (86.2%) and maxillary canines. In conclusion, the SFTE was the common characteristics of most genetic diseases with abnormal isolated or syndromic tooth eruption. The selective pattern of unerupted teeth was gene-dependent. Here we recommend SFTE to classify those genetic unerupted teeth and guide for precise molecular diagnosis and treatment.
Topics: Humans; Tooth Eruption; Tooth, Unerupted; Core Binding Factor Alpha 1 Subunit; Tooth Abnormalities; Phenotype; Genotype; Chloride Channels
PubMed: 37448157
DOI: 10.1111/cge.14400 -
Trends in Ecology & Evolution Dec 2021Epigenetic inheritance is another piece of the puzzle of nongenetic inheritance, although the prevalence, sources, persistence, and phenotypic consequences of heritable... (Review)
Review
Epigenetic inheritance is another piece of the puzzle of nongenetic inheritance, although the prevalence, sources, persistence, and phenotypic consequences of heritable epigenetic marks across taxa remain unclear. We systematically reviewed over 500 studies from the past 5 years to identify trends in the frequency of epigenetic inheritance due to differences in reproductive mode and germline development. Genetic, intrinsic (e.g., disease), and extrinsic (e.g., environmental) factors were identified as sources of epigenetic inheritance, with impacts on phenotype and adaptation depending on environmental predictability. Our review shows that multigenerational persistence of epigenomic patterns is common in both plants and animals, but also highlights many knowledge gaps that remain to be filled. We provide a framework to guide future studies towards understanding the generational persistence and eco-evolutionary significance of epigenomic patterns.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Epigenomics; Germ Cells; Inheritance Patterns; Phenotype
PubMed: 34489118
DOI: 10.1016/j.tree.2021.08.006 -
Neuropediatrics Oct 2023Autosomal dominant mutations of the gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE)....
BACKGROUND
Autosomal dominant mutations of the gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.
METHODS
We searched on PubMed using the search terms "" AND "therapy" and "" AND "treatment"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.
RESULTS
In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).
CONCLUSION
Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a "benign" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.
Topics: Child; Infant, Newborn; Humans; Retrospective Studies; KCNQ2 Potassium Channel; Epilepsy, Benign Neonatal; Mutation; Seizures; Phenotype; Genotype; Phenobarbital
PubMed: 36948217
DOI: 10.1055/a-2060-4576 -
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 -
Journal of Neurology Jun 2021The hereditary spastic paraplegias (HSPs) are a heterogeneous group of inherited neurodegenerative disorders. Although, several genotype-phenotype studies have carried... (Meta-Analysis)
Meta-Analysis Review
AIMS
The hereditary spastic paraplegias (HSPs) are a heterogeneous group of inherited neurodegenerative disorders. Although, several genotype-phenotype studies have carried out on HSPs, the association between genotypes and clinical phenotypes remain incomplete since most studies are small in size or restricted to a few genes. Accordingly, this study provides the systematic meta-analysis of genotype-phenotype associations in HSP.
METHODS AND RESULTS
We retrieved literature on genotype-phenotype associations in patients with HSP and mutated SPAST, REEP1, ATL1, SPG11, SPG15, SPG7, SPG35, SPG54, SPG5. In total, 147 studies with 13,570 HSP patients were included in our meta-analysis. The frequency of mutations in SPAST (25%) was higher than REEP1 (3%), as well as ATL1 (5%) in AD-HSP patients. As for AR-HSP patients, the rates of mutations in SPG11 (18%), SPG15 (7%) and SPG7 (13%) were higher than SPG5 (5%), as well as SPG35 (8%) and SPG54 (7%). The mean age of AD-HSP onset for ATL1 mutation-positive patients was earlier than patients with SPAST, REEP1 mutations. Also, the tendency toward younger age at AR-HSP onset for SPG35 was higher than other mutated genes. It is noteworthy that the mean age at HSP onset ranged from infancy to adulthood. As for the gender distribution, the male proportion in SPG7-HSP (90%) and REEP1-HSP (78%) was markedly high. The frequency of symptoms was varied among patients with different mutated genes. The rates of LL weakness, superficial sensory abnormalities, neuropathy, and deep sensory impairment were noticeably high in REEP1 mutations carriers. Also, in AR-HSP patients with SPG11 mutations, the presentation of symptoms including pes cavus, Neuropathy, and UL spasticity was higher.
CONCLUSION
Our comprehensive genotype-phenotype assessment of available data displays that the mean age at disease onset and particular sub-phenotypes are associated with specific mutated genes which might be beneficial for a diagnostic procedure and differentiation of the specific mutated genes phenotype among diverse forms of HSP.
Topics: Adult; Genetic Association Studies; Genotype; Humans; Male; Membrane Transport Proteins; Mutation; Phenotype; Proteins; Spastic Paraplegia, Hereditary; Spastin
PubMed: 31745725
DOI: 10.1007/s00415-019-09633-1 -
BMC Psychiatry Sep 2023Perinatal depression (PND) is a significant contributor to maternal morbidity globally. Recognized as a major cause of poor infant development, epidemiological and... (Meta-Analysis)
Meta-Analysis
Perinatal depression (PND) is a significant contributor to maternal morbidity globally. Recognized as a major cause of poor infant development, epidemiological and interventional research on it has increased over the last decade. Recently, studies have pointed out that PND is a heterogeneous condition, with variability in its phenotypes, rather than a homogenous latent entity and a concrete diagnosis, as previously conceptualized in psychometric literature and diagnostic systems. Therefore, it is pertinent that researchers recognize this to progress in elucidating its aetiology and developing efficacious interventions.This systematic review is conducted in accordance with the Meta-analysis of observational studies in epidemiology (MOOSE). It aims to provide an updated and comprehensive account of research on heterogeneity in phenotypes of PND and its implications in research, public health, and clinical practice. It provides a synthesis and quality assessment of studies reporting heterogeneity in PND using cutting-edge statistical techniques and machine learning algorithms. After reporting the phenotypes of PND, based on heterogeneous trajectories and symptom profiles, it also elucidates the risk factors associated with severe forms of PND, followed by robust evidence for adverse child outcomes. Furthermore, recommendations are made to improve public health and clinical practice in screening, diagnosis, and treatment of PND.
Topics: Female; Pregnancy; Humans; Depression; Depressive Disorder; Algorithms; Machine Learning; Phenotype; Observational Studies as Topic
PubMed: 37667216
DOI: 10.1186/s12888-023-05121-z -
Journal of Psychiatric Research Aug 2023Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic... (Review)
Review
BACKGROUND
Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic expression. G × E has been studied in the occurrence and development of many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD).
AIM
A systematic review was conducted to investigate the role of G × E plays in OCD. This review explored the relationship between G × E and the susceptibility to OCD occurrence, disease progression, and treatment response.
METHODS
This systematic literature search was performed using Web of Science, PubMed, Cochrane Library, and CNKI. Seven studies were selected, which included seven genes (BDNF, COMT, MAO, 5-HTT, SMAD4, PGRN, and SLC1A1) polymorphisms, polygenic risk score (PRS), and two environmental factors (childhood trauma and stressful life events).
RESULTS
Information from this systematic review indicated that G × E increased the susceptibility to OCD, played a crucial role in the clinical characteristics, and had an inconsistent impact on treatment response of OCD.
FUTURE DIRECTIONS
The multi-omics studies and the inclusion of G × E in future GWAS studies of OCD should be drawn more attention, which may contribute to a deeper understanding of the etiology of OCD as well as guide therapeutic interventions for the disease.
Topics: Humans; Gene-Environment Interaction; Genotype; Genetic Predisposition to Disease; Obsessive-Compulsive Disorder; Polymorphism, Genetic
PubMed: 37390623
DOI: 10.1016/j.jpsychires.2023.06.004 -
Joint Bone Spine Jul 2023Giant Cell Arteritis (GCA) is a heterogenous systemic granulomatous vasculitis involving the aorta and any of its major tributaries. Despite increased awareness of large... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Giant Cell Arteritis (GCA) is a heterogenous systemic granulomatous vasculitis involving the aorta and any of its major tributaries. Despite increased awareness of large vessel (LV) involvement, studies reporting incidence, clinical characteristics and complications of large-vessel GCA (LV-GCA) show conflicting results due to inconsistent disease definitions, differences in study methodologies and the broad spectrum of clinical presentations. The aim of this systematic literature review was to better define LV-GCA based on the available literature and identify distinguishing characteristics that may differentiate LV-GCA patients from those with limited cranial disease.
METHODS
Published studies indexed in MEDLINE and EMBASE were searched from database inception to 7th May 2021. Studies were included if they presented cohort or cross-sectional data on a minimum of 25 patients with LV-GCA. Control groups were included if data was available on patients with limited cranial GCA (C-GCA). Data was quantitatively synthesised with application of a random effects meta-regression model, using Stata.
RESULTS
The search yielded 3488 studies, of which 46 were included. Diagnostic criteria for LV-GCA differed between papers, but was typically dependent on imaging or histopathology. Patients with LV-GCA were generally younger at diagnosis compared to C-GCA patients (mean age difference -4.53 years), had longer delay to diagnosis (mean difference 3.03 months) and lower rates of positive temporal artery biopsy (OR: 0.52 [95% CI: 0.3, 0.91]). Fewer LV-GCA patients presented with cranial manifestations and only 53% met the 1990 ACR Classification Criteria for GCA. Vasculitis was detected most commonly in the thoracic aorta, followed by the subclavian, brachiocephalic trunk and axillary arteries. The mean cumulative prednisolone dose at 12-months was 6056.5mg for LV-GCA patients, relapse rates were similar between LV- and C-GCA patients, and 12% of deaths in LV-GCA patients could be directly attributed to an LV complication.
CONCLUSION
Patients with LV-GCA have distinct disease features when compared to C-GCA, and this has implications on diagnosis, treatment strategies and surveillance of long-term sequalae.
Topics: Humans; Giant Cell Arteritis; Cross-Sectional Studies; Phenotype
PubMed: 36858169
DOI: 10.1016/j.jbspin.2023.105558 -
Vaccine Mar 2022Invasive meningococcal disease (IMD) is a notifiable disease in Germany and other European countries. Due to the high lethality of the disease and the risk of long-term... (Review)
Review
INTRODUCTION
Invasive meningococcal disease (IMD) is a notifiable disease in Germany and other European countries. Due to the high lethality of the disease and the risk of long-term consequences, IMD prevention is of high public health relevance despite the low number of cases in the population. This study aims to describe key epidemiological and economic parameters of IMD in Germany to support national decision-making processes for implementing enhanced prevention measures.
METHODS
Based on a systematic literature review in PubMed and EMBASE, all publications on the burden of disease and costs of IMD published up to May 2020 were evaluated. Additionally, notification data were used to report the annual case numbers and incidence of IMD in Germany until the end of 2019.
RESULTS
Thirty-six studies were included, of which 35 reported data on the epidemiological burden of disease and three reported data on economic aspects of IMD. The type of reported endpoints and results on the incidence of IMD differed widely by reporting year, population, and data source used. Most of the data are reported without specific information about a serogroup. Data on the economic burden of disease and healthcare resource use are scarce. Based on mandatory notification data, a decrease in the incidence of notified IMD cases has been observed since 2004. Currently, the nationwide annual incidence in Germany is at 0.3 cases per 100,000 persons and has gradually decreased. While the overall decline is mainly attributable to MenB, cases with MenY and MenW are the only ones that have increased on a low level in recent years.
CONCLUSION
While IMD is a rare disease, high direct and indirect costs illustrate the relevance of the disease for patients, caregivers, as well as for the health care system. Future research should concentrate on quantifying the long-term economic burden and indirect costs of meningococcal disease. Integrated IMD surveillance with isolate characterisation remains crucial to inform public health policies.
Topics: Financial Stress; Germany; Humans; Incidence; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Serogroup
PubMed: 35227520
DOI: 10.1016/j.vaccine.2022.02.043 -
Journal of Medical Internet Research Dec 2023The COVID-19 pandemic has increased the impact and spread of mental illness and made health services difficult to access; therefore, there is a need for remote,... (Review)
Review
BACKGROUND
The COVID-19 pandemic has increased the impact and spread of mental illness and made health services difficult to access; therefore, there is a need for remote, pervasive forms of mental health monitoring. Digital phenotyping is a new approach that uses measures extracted from spontaneous interactions with smartphones (eg, screen touches or movements) or other digital devices as markers of mental status.
OBJECTIVE
This review aimed to evaluate the feasibility of using digital phenotyping for predicting relapse or exacerbation of symptoms in patients with mental disorders through a systematic review of the scientific literature.
METHODS
Our research was carried out using 2 bibliographic databases (PubMed and Scopus) by searching articles published up to January 2023. By following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines, we started from an initial pool of 1150 scientific papers and screened and extracted a final sample of 29 papers, including studies concerning clinical populations in the field of mental health, which were aimed at predicting relapse or exacerbation of symptoms. The systematic review has been registered on the web registry Open Science Framework.
RESULTS
We divided the results into 4 groups according to mental disorder: schizophrenia (9/29, 31%), mood disorders (15/29, 52%), anxiety disorders (4/29, 14%), and substance use disorder (1/29, 3%). The results for the first 3 groups showed that several features (ie, mobility, location, phone use, call log, heart rate, sleep, head movements, facial and vocal characteristics, sociability, social rhythms, conversations, number of steps, screen on or screen off status, SMS text message logs, peripheral skin temperature, electrodermal activity, light exposure, and physical activity), extracted from data collected via the smartphone and wearable wristbands, can be used to create digital phenotypes that could support gold-standard assessment and could be used to predict relapse or symptom exacerbations.
CONCLUSIONS
Thus, as the data were consistent for almost all the mental disorders considered (mood disorders, anxiety disorders, and schizophrenia), the feasibility of this approach was confirmed. In the future, a new model of health care management using digital devices should be integrated with the digital phenotyping approach and tailored mobile interventions (managing crises during relapse or exacerbation).
Topics: Humans; Mental Disorders; Mental Health; Mood Disorders; Pandemics; Recurrence; Smartphone
PubMed: 38090800
DOI: 10.2196/46778