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Neuropsychology Review Dec 2023Williams syndrome (WS) is a neurodevelopmental disorder caused by a microdeletion in the q11.23 region of chromosome 7. Recent case series reports and clinical case... (Review)
Review
Williams syndrome (WS) is a neurodevelopmental disorder caused by a microdeletion in the q11.23 region of chromosome 7. Recent case series reports and clinical case studies have suggested that the cognitive, behavioral, emotional, and social profile in WS could depend on the genes involved in the deletion. The objective of this systematic review was to analyze and synthesize the variability of the cognitive and behavioral profile of WS with atypical deletion and its probable relationship with the affected genes. The medical subject headings searched were "Williams syndrome," "genotype," "phenotype," "cognitive profile," and "atypical deletion." The studies included were in English or Spanish, with children and adults, and published between January 2000 and October 2022. Twenty-three studies are reported. The characteristics of the participants, the genes involved, the neuropsychological domains and instruments, and the prevalence of the WS cognitive profile criteria were used for the genotype-phenotype analysis. The genes with a major impact on the cognitive profile of WS were (a) LIMK1 and those belonging to the GTF2I family, the former with a greater influence on visuospatial abilities; (b) GTF2IRD1 and GTF2I, which have an impact on intellectual capacity as well as on visuospatial and social skills; (c) FZD9, BAZ1B, STX1A, and CLIP2, which influence the cognitive profile if other genes are also effected; and (d) GTF2IRD2, which is related to the severity of the effect on visuospatial and social skills, producing a behavioral phenotype like that of the autism spectrum. The review revealed four neuropsychological phenotypes, depending on the genes involved, and established the need for more comprehensive study of the neuropsychological profile of these patients. Based on the results found, we propose a model for the investigation of and clinical approach to the WS neuropsychological phenotype.
Topics: Child; Adult; Humans; Williams Syndrome; Genotype; Phenotype; Neurodevelopmental Disorders; Transcription Factors, TFIII; Lim Kinases; Bromodomain Containing Proteins; Transcription Factors
PubMed: 36520254
DOI: 10.1007/s11065-022-09571-2 -
Non-coding RNA Jul 2023MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been... (Review)
Review
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles in human disease. First identified as an aging-associated gene in , miR-71, a miRNA, has a demonstrated capability of regulating processes in numerous different invertebrates, including platyhelminths, mollusks, and insects. In these organisms, miR-71 has been shown to affect a diverse range of pathways, including aging, development, and immune response. However, the exact mechanisms by which miR-71 regulates these pathways are not completely understood. In this paper, we review the identified functions of miR-71 across multiple organisms, including identified gene targets, pathways, and the conditions which affect regulatory action. Additionally, the degree of conservation of miR-71 in the evaluated organisms and the conservation of their predicted binding sites in target 3' UTRs was measured. These studies may provide an insight on the patterns, interactions, and conditions in which miR-71 is able to exert genotypic and phenotypic influence.
PubMed: 37624033
DOI: 10.3390/ncrna9040041 -
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 -
Tropical Medicine and Infectious Disease Sep 2023The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy... (Review)
Review
The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against infection. However, recent studies suggest that this microorganism's evolution could potentially diminish this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. The Medline/PubMed, Web of Science, Scopus, and SciELO databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for the majority of recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with In conclusion, this systematic review found that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of infection. Furthermore, the negative Duffy genotype does not confer protection against vivax malaria.
PubMed: 37888591
DOI: 10.3390/tropicalmed8100463 -
Critical Reviews in Oncology/hematology Aug 2023Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian,... (Review)
Review
Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian, gastric, biliary duct cancers and glioblastoma. Though not classically associated with LS, growing literature suggests that sarcomas might develop in patients with LS. This systematic review of literature identified 44 studies (N = 95) of LS patients who developed sarcomas. It seems that most sarcomas developed in patients with a germline mutation of MSH2 (57 %) exhibit a dMMR (81 %) or MSI (77 %) phenotype, as in other LS-tumors. Although undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma, and liposarcoma remain the most represented histologic subtype, a higher proportion of rhabdomyosarcoma (10 %, especially pleomorphic rhabdomyosarcoma) is reported. Further studies are required to better characterize this sub-population.
Topics: Humans; Colorectal Neoplasms, Hereditary Nonpolyposis; Colorectal Neoplasms; Genetic Predisposition to Disease; Germ-Line Mutation; Sarcoma; Rhabdomyosarcoma; DNA Mismatch Repair; Microsatellite Instability
PubMed: 37301271
DOI: 10.1016/j.critrevonc.2023.104055 -
Pain Reports Dec 2023To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science... (Review)
Review
To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science for original studies reporting or investigating at least one subtype within a group of patients with CRPS. The search retrieved 4239 potentially relevant references. Twenty-five studies met our inclusion criteria and were included in the analysis. Complex regional pain syndrome phenotypes were investigated based on the following variables: clinical presentation/sensory disturbances, dystonia, skin temperature, disease duration, onset type, CRPS outcome, and neuropsychological test performance. Support was found for the following CRPS subtypes: CRPS type I, CRPS type II, acute CRPS, chronic CRPS, centralized CRPS, cold CRPS, warm CRPS, inflammatory CRPS, dystonic CRPS, nondystonic CRPS, familial CRPS, and nonfamilial CRPS. It is unclear whether these are distinct or overlapping subtypes. The results of this comprehensive review can facilitate the formulation of well-defined CRPS subtypes based on presumed underlying mechanisms. Our findings provide a foundation for establishing and defining clinically meaningful CRPS subtypes, with the ultimate goal of developing targeted and enhanced treatments for CRPS.
PubMed: 38027463
DOI: 10.1097/PR9.0000000000001111 -
Frontiers in Endocrinology 2023PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of pregnancy loss in PCOS. However, uncertainty remains about their contribution to pregnancy loss and prognosis. This review of literature aims to identify what is known and what requires further investigation on the relationship between PCOS and recurrent pregnancy loss, to guide future research and optimize medical guidance throughout pregnancy.
STUDY DESIGN
a review of literature was performed on several search engines using the following terms; polycystic ovarian syndrome, PCOS, recurrent pregnancy loss, recurrent miscarriage, RPL, aborted fetus, abortus provocatus, miscarriage and habitual abortion.
RESULTS
37 articles were included; 3 systematic reviews, 1 meta-analysis, 2 randomized controlled trials, 6 prospective cohort studies, 22 case-control studies and 3 case series. The main objectives investigated by studies were pregnancy complications, pregnancy loss and live birth in the PCOS population.
CONCLUSION
Studies that investigated the relationship between PCOS and recurrent pregnancy loss are few and inconsistent and warrant further research. Factors apt for further investigation include the extent to which PCOS phenotypes, BMI, obesity, insulin resistance, hyperandrogenemia, SHBG, hs-CRP, CTRP6, adiponectin, plasma leptin, homocysteine, AMH and thrombophilia contribute to further risk of miscarriage. Other factors requiring further exploration in relation to risk for miscarriage in PCOS patient with RPL include sOB-R, PAI-Fx and the Factor-V-Leiden mutations.
Topics: Pregnancy; Female; Humans; Polycystic Ovary Syndrome; Prospective Studies; Abortion, Habitual; Thrombophilia; Obesity
PubMed: 38027110
DOI: 10.3389/fendo.2023.1183060 -
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 -
Diabetologia Apr 2024Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of... (Meta-Analysis)
Meta-Analysis Review
Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.
Topics: Adult; Humans; Heart Failure; Diabetes Mellitus, Type 2; Stroke Volume; Prognosis; Disease Progression
PubMed: 38334818
DOI: 10.1007/s00125-023-06068-2 -
Artificial intelligence for diagnostic and prognostic neuroimaging in dementia: A systematic review.Alzheimer's & Dementia : the Journal of... Dec 2023Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. (Review)
Review
INTRODUCTION
Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia.
METHODS
We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases.
RESULTS
A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort.
DISCUSSION
The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice.
HIGHLIGHTS
There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias.
Topics: Humans; Alzheimer Disease; Prognosis; Artificial Intelligence; Neurodegenerative Diseases; Brain; Neuroimaging
PubMed: 37563912
DOI: 10.1002/alz.13412