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Pediatric Surgery International Aug 2017Hirschsprung's disease (HSCR) is known to occur in families. The reported overall incidence of familial cases is 7.6%, with a higher incidence of 15-21% in total colonic... (Meta-Analysis)
Meta-Analysis Review
AIM OF THE STUDY
Hirschsprung's disease (HSCR) is known to occur in families. The reported overall incidence of familial cases is 7.6%, with a higher incidence of 15-21% in total colonic aganglionosis and 50% in the rare total intestinal aganglionosis. HSCR is extremely rare in twins. The aim of this study was to systematically analyse the patterns of HSCR in twins published in the literature.
METHODS
Electronic databases Pubmed and Medline were screened for relevant articles using the keywords "Hirschsprung's disease", "aganglionosis", "twins", "monozygotic", and "dizygotic". Examining reference lists identified further relevant papers.
MAIN RESULTS
Twelve studies with a total of 18 twin pairs were included in this analysis. 67% twins were discordant. HSCR was found in 24 out of 36 twin subjects (67%), of which 83% affected were male. Rectosigmoid type was reported in 71% of patients, long-segment disease in 21, and 8% presented with a total aganglionosis. Three twin pairs had at least one family member affected with HSCR.
CONCLUSION
HSCR was found in two-thirds of twin subjects with a male predominance. Rectosigmoid aganglionosis was the most common variant. Disease discordance was identified, where environmental insults were postulated to be predisposing factors to disease expression. Future studies investigating the disease-associated mutations in the already identified HSCR genes should provide insights into the genetic basis of HSCR in twins.
Topics: Diseases in Twins; Female; Hirschsprung Disease; Humans; Incidence; Male; Twins
PubMed: 28601901
DOI: 10.1007/s00383-017-4110-7 -
Journal of the American Society of... Nov 2014Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families.... (Review)
Review
Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
Topics: Disease Progression; Humans; Kidney; Polycystic Kidney, Autosomal Dominant; Predictive Value of Tests; TRPP Cation Channels
PubMed: 24925719
DOI: 10.1681/ASN.2013111184 -
Blood Apr 2016Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course... (Meta-Analysis)
Meta-Analysis Review
Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course has been well recognized. The Rai and Binet staging systems described ∼40 years ago have proven to be robust prognostic tools. Over the past 2 decades, several novel biological, genetic, and molecular markers have been shown to be useful adjuncts to the Rai and Binet staging systems. In this systematic review, we examined the role of immunoglobulin heavy-chain variable region gene (IGHV) mutation status and genetic abnormalities determined by interphase fluorescence in situ hybridization (FISH) in patients with newly diagnosed CLL. The cumulative evidence presented in this systematic review is sufficient to recommend that FISH and IGHV be performed as standard clinical tests for all patients with newly diagnosed CLL in those countries with the resources to do so. In addition to clinical stage, these parameters could represent the minimal standard initial prognostic evaluation for patients with CLL. This approach will allow the application of powerful, recently developed prognostic indices (all of which are dependent on IGHV and FISH results) to all patients with newly diagnosed CLL.
Topics: Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Prognosis
PubMed: 26841802
DOI: 10.1182/blood-2015-10-620864 -
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 -
American Journal of Clinical Dermatology Apr 2015Epidermolysis bullosa pruriginosa (EBP) is a clinical variant of dystrophic epidermolysis bullosa (DEB), characterized by intense pruritus and hypertrophic, lichenified,... (Review)
Review
INTRODUCTION
Epidermolysis bullosa pruriginosa (EBP) is a clinical variant of dystrophic epidermolysis bullosa (DEB), characterized by intense pruritus and hypertrophic, lichenified, prurigo-like papules, plaques, and nodules secondary to scratching. These clinical findings have been attributed to various mutations in the COL7A1 gene. Previous reports have yielded inconsistent findings regarding a possible genotype-phenotype relationship in EBP.
OBJECTIVE
Our aim was to conduct a systematic review aimed at assessing the genotype-phenotype correlation in EBP.
METHODS
A systematic review was conducted using PubMed, Medline, EMBASE, and Cochrane databases for all reports of mutation-verified EBP, published from 1946 to September 2014. Statistical comparison of clinical findings between mutation types was performed using logistic regression analysis.
RESULTS
The review included a total of 28 articles with 74 individuals, which consisted of level 4 non-controlled case series (grade C) and level 5 case reports (grade D). Previous reported mutation types included glycine substitution (GS, 52.7%), in-frame skipping (IFS, 33.8%), non-glycine substitution (NGS, 8.1%), and premature termination codon (PTC, 5.4%). The most common clinical findings were extremities involvement, linear configuration, and nail dystrophy. In comparison with GS mutation carriers, IFS carriers had a higher likelihood of (1) being male (OR 2.99; p = 0.043; 95% CI 1.27-11.4) and (2) presenting with blisters (OR 4.10; p = 0.013; 95% CI 1.34-12.5).
CONCLUSIONS
To our knowledge, this study is the first systematic review examining the relationship between mutation type and clinical presentation in EBP. The findings in this review (1) identify common clinical characteristics of EBP that may help in the assessment of patients with possible EBP; and (2) indicate that certain mutation carriers may have a higher likelihood of exhibiting particular phenotypes. In the case of potential diagnostic challenge, assessment for presence of common clinical findings as well as molecular testing may facilitate correct identification and prognostication.
Topics: Age of Onset; Epidermolysis Bullosa Dystrophica; Genotype; Humans; Mutation; Phenotype
PubMed: 25690953
DOI: 10.1007/s40257-015-0119-7 -
Journal of Pharmacy & Bioallied Sciences Jun 2021Cellular signaling proteins maintain the basic activities of cell and communication, between the cells for normal growth and development and pathological situation as... (Review)
Review
Cellular signaling proteins maintain the basic activities of cell and communication, between the cells for normal growth and development and pathological situation as well. Fibroblast growth factor (FGF) and fibroblast growth factor receptors (FGFRs) have a comparatively huge part to play in the cellular communication processes. Human FGF has 22 members, 18 ligands, and 4 tyrosine kinase receptors for binding and is expressed in a wide range of cells. Any alteration in these factors would disrupt their normal function, leading to various abnormalities. The aim of this systematic analysis, is to understand the FGFs, the physiological and pathological role of FGF in oral diseases, and to predict the use of FGF in the predilection toward odontogenic cyst and tumors. This review helps confer the role of FGF in various physiological and pathological aspects in systemic diseases and analyzes its role in diagnosis and prognosis of odontogenic cysts and tumors.
PubMed: 34447033
DOI: 10.4103/jpbs.JPBS_563_20 -
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 -
Journal of Neural Transmission (Vienna,... Jun 2021Based on recent evidence, more than 200 susceptibility genes have been identified to be associated with autism until now. Correspondingly, cytogenetic abnormalities have...
BACKGROUND
Based on recent evidence, more than 200 susceptibility genes have been identified to be associated with autism until now. Correspondingly, cytogenetic abnormalities have been reported for almost every chromosome. While the results of multiple genes associated with risk factors for autism are still incomplete, this paper systematically reviews published meta-analyses and systematic reviews of evidence related to autism occurrence.
METHOD
Literature search was conducted in the PubMed system, and the publication dates were limited between January 2000 and July 2020. We included a meta-analysis and systematic review that assessed the impact of related gene variants on the development of autism. After screening, this comprehensive literature search identified 31 meta-analyses and ten systematic reviews. We arranged the genes related to autism in the published studies according to the order of the chromosomes, and based on the results of a meta-analysis and systematic review, we selected 6 candidate genes related to ASD, namely MTHFR C677T, SLC25A12, OXTR, RELN, 5-HTTLPR, SHANK, including basic features and functions. In addition to these typical genes, we have also listed candidate genes that may exist on almost every chromosome that are related to autism.
RESULTS
We found that the results of several literature reviews included in this study showed that the MTHFR C667T variant was a risk factor for the occurrence of ASD, and the results were consistent. The results of studies on SLC25A12 variation (rs2056202 and rs2292813) and ASD risk were inconsistent but statistically significant. No association of 5-HTTLPR was found with autism, but when subgroup analysis was performed according to ethnicity, the association was statistically significant. RELN variants (rs362691 and rs736707) were consistent with ASD risk studies, but some of the results were not statistically significant.
CONCLUSION
This review summarized the well-known ASD candidate genes and listed some new genes that need further study in larger sample sets to improve our understanding of the genetic basis of ASD, but sample size and heterogeneity remain major limiting factors in some genome-wide association studies. We also found that common genetic variants in some genes may be co-risk factors for autism or other neuropsychiatric disorders when we collated these results. It is worth considering screening for these mutations in clinical applications.
Topics: Autism Spectrum Disorder; Autistic Disorder; Genome-Wide Association Study; Humans; Meta-Analysis as Topic; Methylenetetrahydrofolate Reductase (NADPH2); Reelin Protein; Risk Factors; Systematic Reviews as Topic
PubMed: 34115189
DOI: 10.1007/s00702-021-02360-w -
Prenatal Diagnosis Aug 2023Unexplained stillbirth is defined as a stillbirth with no known cause after the exclusion of common causes, including obstetric complications, infections, placental... (Review)
Review
Unexplained stillbirth is defined as a stillbirth with no known cause after the exclusion of common causes, including obstetric complications, infections, placental insufficiency or abruption, umbilical cord complications, and congenital abnormalities with or without known genetic cause. More than 60% of stillbirth cases remain unexplained. The aim of this systematic review was to investigate the known genetic causes of unexplained stillbirth cases and to evaluate the current position and future directions for the use of genetic and genomic testing in expanding the knowledge in this field. A systematic search through several databases was performed using the keywords genetics and stillbirths in humans. Different methods to detect various types of causal genetic aberrations have been used in the past decades, from standard karyotyping to novel methods such as chromosomal microarray analysis and next generation sequencing technologies. Apart from common chromosomal aneuploidies, a promising hypothesis about genetic causes included genes related to cardiomyopathies and channelopathies. However, these were tested in the research settings, since molecular karyotyping is currently the standard approach in the routine evaluation of genetic causes of stillbirth. Hereby, we provide evidence that expanding knowledge using novel genetic and genomic testing might uncover new genetic causes of unexplained stillbirth.
Topics: Humans; Female; Pregnancy; Stillbirth; Placenta; Aneuploidy; Databases, Factual; Genetic Profile
PubMed: 37072878
DOI: 10.1002/pd.6354 -
Birth Defects Research. Part C, Embryo... Dec 2014Congenital anorectal malformations (ARMs) are one of the most frequently observed birth defects of the digestive system. However, their etiology remains elusive.... (Review)
Review
Congenital anorectal malformations (ARMs) are one of the most frequently observed birth defects of the digestive system. However, their etiology remains elusive. Therefore, we aim to summarize and critically appraise all existing literature on the genetic and nongenetic etiology of nonsyndromic ARM and to conclude with unifying hypotheses and directions for future research. A structured literature search on English language human studies was conducted in PubMed and Embase up to October 1, 2013, resulting in 112 included articles. Research on the identification of genes underlying nonsyndromic ARM is remarkably scarce. Most studies were focused on screening of candidate genes for mutations or single-nucleotide polymorphisms, which did not yield any substantial evidence. Nongenetic factors fairly consistently found to be associated with ARM are assisted reproductive techniques, multiple pregnancy, preterm delivery, low birth weight, maternal overweight or obesity, and preexisting diabetes. This review provides indications for the involvement of both genes and nongenetic risk factors in the etiology of ARM. In future studies, large cohorts of patients with ARM from national and international collaborations are needed to acquire new hypotheses and knowledge through hypothesis-generating approaches. Challenges for future studies may also lie in the investigation of gene-gene and gene-environment interactions.
Topics: Anal Canal; Anorectal Malformations; Anus, Imperforate; Female; Humans; Pregnancy; Rectum
PubMed: 25546370
DOI: 10.1002/bdrc.21068