-
Orphanet Journal of Rare Diseases Aug 2019Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50-60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power.
RESULTS
Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (OR: 0.654 [0.408-1.046]; OR : 1.291 [0.860-1.939]) or palate anomalies (OR: 1.731 [0.708-4.234]; OR : 0.628 [0.286-1.382]).
CONCLUSIONS
The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes.
Topics: Arachnodactyly; Chromosome Deletion; Craniosynostoses; Humans; Marfan Syndrome; Phenotype
PubMed: 31399107
DOI: 10.1186/s13023-019-1170-x -
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 -
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 -
Archives of Oral Biology Jan 2022To conduct a systematic review and meta-analysis of studies that evaluated the association between gingival phenotype (GP) and the underlying alveolar bone thickness... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review and meta-analysis of studies that evaluated the association between gingival phenotype (GP) and the underlying alveolar bone thickness (ABT).
DESIGN
An electronic search was performed in PubMed, Embase, Scopus, ProQuest, and Web of Science. The following inclusion criteria were applied: English original studies that compared the ABT in periodontally healthy patients presenting thin versus thick GPs. Studies that evaluated the correlation between gingival thickness (GT) and ABT were also included. Pooled mean difference (95% confidence interval) was estimated using random-effects maximum likelihood model meta-analysis.
RESULTS
From a total of 1427 retrieved articles, 17 were included. The majority of eight studies that compared the ABT between thick and thin GPs, reported a significantly greater ABT associated with a thick phenotype. Based on the meta-analysis results of six studies, the mean difference between the two phenotypes (0.33 mm) was statistically significant (P < 0.01). The majority of ten studies that investigated the correlation between GT and ABT evidenced a significant positive correlation (r = 0.11 -0.49). The association was more evident in the crestal areas and decreased toward the apex.
CONCLUSIONS
There is contradictory evidence concerning the correlation between soft and hard tissue thickness; however, the meta-analysis revealed a significantly thicker alveolar plate in the presence of a thick phenotype. Since the evaluation of GP could be simply performed using a periodontal probe, such a relationship could provide clinical perspective at the initial examination. This is particularly beneficial in procedures affecting periodontal structures, including immediate implant placement and orthodontic treatments.
Topics: Gingiva; Humans; Phenotype
PubMed: 34768057
DOI: 10.1016/j.archoralbio.2021.105287 -
Biotechnology Advances Oct 2023Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves... (Review)
Review
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.
Topics: Temperature; Metabolic Networks and Pathways; Phenotype; Models, Biological
PubMed: 37348662
DOI: 10.1016/j.biotechadv.2023.108203 -
Reviews in Endocrine & Metabolic... Oct 2022Maturity-Onset Diabetes of the Youth (MODY) diabetes remains commonly misdiagnosed. A monogenic form should be suspected in individuals presenting hyperinsulinemic... (Review)
Review
Maturity-Onset Diabetes of the Youth (MODY) diabetes remains commonly misdiagnosed. A monogenic form should be suspected in individuals presenting hyperinsulinemic hypoglycemia (HH) associated with, either later development of MODY (hypoglycemia-remission-diabetes sequence), or with first/second-degree family history of diabetes. Herein, we aimed to describe this individual or family monogenic association between HH and diabetes, and identify potential genotype-phenotype correlations. We conducted a systematic review of 26 studies, including a total of 67 patients with this association resulting from variants in GCK (n = 5 cases), ABCC8 (n = 29), HNF1A (n = 5), or HNF4A (n = 28). A family history of hypoglycemia and/or diabetes was present in 91% of cases (61/67). Median age at first hypoglycemia was 24 h after birth. Diazoxide was initiated in 46 children (46/67-69%); responsiveness was found in 91% (42/46). Median HH duration was three years (1 day-25 years). Twenty-three patients (23/67-34%) later developed diabetes (median age: 13 years; range: 8-48); more frequently in those untreated with diazoxide. This association was most commonly inherited in an autosomal dominant manner (43/48-90%). Some genes were associated with less severe initial hypoglycemia (HNF1A), shorter duration of HH (HNF4A), and more maternal (ABCC8) or paternal (HNF4A) transmission. This study illustrates that the same genotype can give a biphasic phenotype in the same person or a reverse phenotype in the same family. Wider awareness of this association is necessary in pediatrics to establish annual monitoring of patients who have presented HH, and during maternity to screen diabetes and optimize genetic counseling and management of pregnancy, childbirth, and the newborn.PROSPERO registration: CRD42020178265.
Topics: Child; Congenital Hyperinsulinism; Diabetes Mellitus, Type 2; Diazoxide; Female; Humans; Mutation; Phenotype; Pregnancy
PubMed: 35996042
DOI: 10.1007/s11154-022-09749-2 -
European Journal of Obstetrics,... Dec 2022We conducted a systematic review and meta-analyses of the prevalence of Polycystic Ovary Syndrome (PCOS) and the frequency of its phenotypes in Europe and the USA, also... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analyses of the prevalence of Polycystic Ovary Syndrome (PCOS) and the frequency of its phenotypes in Europe and the USA, also focusing on temporal trends of the condition, to compare the PCOS prevalence among populations with a similar level of diagnostic resources availability and attitudes toward health problems, to improve comparability of estimates. We considered Europe and USA, two high-income areas with these characteristics. The overall PCOS prevalence according to the NIH1990, ESHRE/ASRM 2003, AES-PCOS diagnostic criteria was respectively 6.2 % (95%CI 5.3-7.0), 19.5 % (95%CI 17.3-21.6), and 15.0 % (95%CI 12.9-17.1), with no appreciable heterogeneity across geographic areas. Phenotype A, the "complete PCOS", showed higher prevalence in all areas (44.8%, 95%CI 40.3-49.3), followed by phenotype D, called "non-hyperandrogenic PCOS" (19.5%), phenotype C termed as "ovulatory PCOS" (16.2%), and phenotype B, presenting as phenotype A but without polycystic ovarian morphology (14.9%). In all the studies analysing temporal trends of PCOS, an increase in prevalence of PCOS was reported, due, at least in part, to changing diagnostic criteria. The prevalence of PCOS is similar in European countries and the USA. Interestingly, some differences in the frequency of PCOS phenotypes emerged between the two areas with a higher frequency of phenotype A and a lower one of phenotype C in the USA. Recognizing the factors which explain these differences would lead to a better understanding of the etiopathogenesis and the clinical expression of PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Prevalence; Europe; Phenotype
PubMed: 36343588
DOI: 10.1016/j.ejogrb.2022.10.020