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Annals of Human Biology Jun 2021Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of...
CONTEXT
Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of mutations and the prevalence of thalassaemia, but findings are often contradictory.
OBJECTIVE
This systematic review aimed to provide a comprehensive view of the prevalence of thalassaemia-associated mutations in different countries, their effect on haemoglobin (Hb) levels, as well as reporting thalassaemia-associated rare mutations.
METHODS
A systematic search of the literature was carried out through major indexing databases (MEDLINE/PubMed, Scopus, EMBASE, Cochrane central, and ISI web of science) using keywords: "Co-inheritance, αα, β, thalassaemia" and "α-β thalassaemia, Mediterranean anemia, mutations" from 1998-September 2019. Hand-searching was also performed. There was no language restriction.
RESULTS
The initial searches yielded 1059 studies, of which 92 articles were included following inclusion and exclusion criteria. Of these, 3.3% (3) of articles were cohort studies, and 96.7% (89) of the remaining articles were cross-sectional studies. Our findings showed that 45.6% (42) of researchers investigated β-thalassaemia, 22.9% (21) αα-β thalassaemia, and 31.5% (29) α thalassaemia.
CONCLUSION
The present study provides valuable information about the spectrum of thalassaemia-associated mutations, which can be useful for preventing thalassaemia, reducing costs of care, reducing the treatment-related side effects, and showing the most defective mutations.HighlightEvaluating the increase or decrease in the birth prevalence of thalassaemiaIdentifying the most common and rare mutations in various parts of the worldComparing researchers' findings from various parts of the world.
Topics: Humans; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 34032183
DOI: 10.1080/03014460.2021.1909135 -
Leukemia Research Dec 2021
Topics: Genetic Diseases, X-Linked; Humans; Myelodysplastic Syndromes; Myeloproliferative Disorders; alpha-Thalassemia
PubMed: 34325177
DOI: 10.1016/j.leukres.2021.106670 -
Arquivos Brasileiros de Cardiologia Dec 2022Sickle cell anemia (SCA) is a hereditary disease whose cardiovascular complications are the main cause of death, the same being observed in other hemoglobinopathies....
BACKGROUND
Sickle cell anemia (SCA) is a hereditary disease whose cardiovascular complications are the main cause of death, the same being observed in other hemoglobinopathies. Early identification of these changes can favorably modify the course of the disease.
OBJECTIVE
To compare the prevalence of cardiovascular complications between individuals with SCA and individuals with other hemoglobinopathies.
METHOD
Following the recommendations of the PRISMA protocol, a systematic literature review was carried out with searches in PubMed/Medline databases, associated with a manual search. Studies that analyzed the prevalence of cardiovascular alterations in hemoglobinopathies (SCA, sickle cell trait, SC hemoglobinopathy, alpha-thalassemia and beta-thalassemia) were included. The methodological quality of the articles was assessed using the Newcastle-Ottawa scale.
RESULTS
Four studies were selected for analysis, resulting in a sample size of 582 participants: 289 with SCA, 133 with SC hemoglobinopathy, 40 with beta-thalassemia, 100 healthy individuals and none with alpha-thalassemia or sickle cell trait. Dilatation of the cardiac chambers, left and right ventricular hypertrophy, pulmonary hypertension, diastolic dysfunction, mitral regurgitation and tricuspid regurgitation are more prevalent in SCA than in the other hemoglobinopathies considered. Myocardial iron overload is more frequent in thalassemia major than in sickle cell anemia. Systolic function is similar between different hemoglobinopathies.
CONCLUSION
There is greater cardiovascular impairment in individuals with SCA than in those with other hemoglobinopathies, reinforcing the necessity for regular cardiovascular follow-up in sickle cell patients.
Topics: Humans; beta-Thalassemia; Sickle Cell Trait; alpha-Thalassemia; Prevalence; Hemoglobinopathies; Anemia, Sickle Cell
PubMed: 36417618
DOI: 10.36660/abc.20220207 -
Prenatal Diagnosis Nov 2023To clarify the relevance of PIEZO1 variants detected by prenatal exome in the context of non-immune hydrops fetalis (NIHF).
OBJECTIVE
To clarify the relevance of PIEZO1 variants detected by prenatal exome in the context of non-immune hydrops fetalis (NIHF).
METHODS
A systematic review of prenatal exome studies from 1/1/2000-8/1/2022 was performed. Thirty-six studies met the inclusion criteria. PIEZO1 variants were categorized by disease mode (dominant (AD) versus recessive (AR)) and classified by the American College of Medical Genetics and Genomics (ACMG) guidelines.
RESULTS
Twenty-two pregnancies with 35 distinct PIEZO1 variants were included. We deemed PIEZO1 variants to be "likely diagnostic" in 12/22 pregnancies, "possibly diagnostic" in 7/22, and "unlikely diagnostic" in 3/22. In total, 19 of 191 NIHF cases diagnosed by prenatal exome were attributed to PIEZO1. Among likely diagnosed cases, the disease mode was AR in eight and AD in four. PIEZO1 variants causing AR NIHF were characterized by loss of function and isolated NIHF phenotype. PIEZO1 variants causing AD NIHF were characterized by gain of function in red blood cells, scarcity in databases, and sporadic inheritance. Missense variants associated with NIHF were clustered in three domains: transmembrane helical unit 4 (THU4), THU5, and the Cap.
CONCLUSION
PIEZO1 variants were reported in 10% of NIHF cases diagnosed by prenatal exome, making PIEZO1 the most common single gene reported in NIHF.
Topics: Pregnancy; Female; Humans; Hydrops Fetalis; Exome Sequencing; Genomics; Ion Channels
PubMed: 37902181
DOI: 10.1002/pd.6451 -
Obstetrics and Gynecology Dec 2021To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops.
OBJECTIVE
To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops.
DATA SOURCES
PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases were searched using the following keywords: "fetus" OR "foetal" OR "fetal" OR "foetus" AND "ascites" from inception to February 2020. The search was limited to the English language.
METHODS OF STUDY SELECTION
A total of 1,983 articles were identified through the search strategy. All studies containing five or more cases of isolated fetal ascites were included.
TABULATION, INTEGRATION, AND RESULTS
Eleven studies, involving 315 cases of isolated fetal ascites, were eligible for inclusion in this systematic review. All included studies were evaluated using the tool for evaluating the methodologic quality of case reports and case series described by Murad et al. Data were summarized using narrative review and descriptive statistics. Two-tailed Fisher exact P values calculated from hypergeometric distribution were used to compare outcome by etiology. CIs were calculated with Clopper-Pearson exact binomial interval. The etiologies of isolated fetal ascites are genitourinary (24%), gastrointestinal (20%), viral or bacterial infections (9%), cardiac (9%), genetic disorders not otherwise categorized (8%), chylous ascites (6%), metabolic storage disorders (3%), other structural disorders (4%), other causes (4%) and idiopathic (13%). Survival is most favorable for cases of isolated fetal ascites as a result of chylous (100%), idiopathic (90%), gastrointestinal (77%) and genitourinary (77%) etiologies. Survival is least favorable for fetuses with isolated fetal ascites as a result of structural disorders (25%), cardiac etiology (32%) and metabolic storage disorders (33.3%). When pregnancy terminations were excluded, survival rates were similar between fetuses diagnosed at or after 24 weeks of gestation compared with those diagnosed at less than 24 weeks (74% vs 61%, P=.06). Progression of fetal ascites to fetal hydrops occurred in 6.6% (95% CI 3.6-9.6%) (17/259) of cases when pregnancies that were terminated were excluded.
CONCLUSION
Isolated fetal ascites has a diverse etiology. Outcome is related to the etiology of isolated fetal ascites. In the majority of cases, fetal ascites does not progress to fetal hydrops.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42020213930.
Topics: Ascites; Disease Progression; Female; Fetal Death; Fetal Diseases; Gestational Age; Humans; Hydrops Fetalis; Pregnancy; Pregnancy Outcome; Survival Rate
PubMed: 34735407
DOI: 10.1097/AOG.0000000000004605 -
Orphanet Journal of Rare Diseases Jun 2022Meta-analysis was used to evaluate the diagnostic value of a CVR cut-off value of 1.6 for fetal hydrops due to congenital lung malformation (CLM). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Meta-analysis was used to evaluate the diagnostic value of a CVR cut-off value of 1.6 for fetal hydrops due to congenital lung malformation (CLM).
METHODS
A systematic search of PubMed, Embase, Web of Science, CNKI, VIP, and Wanfang published before 7/30/2021 for the value of a congenital pulmonary airway malformation volume ratio (CVR) cut-off value of 1.6 for the diagnosis of fetal hydrops. According to the inclusion and exclusion criteria, the literature that met the requirements were obtained. A total of 75 articles were retrieved, and 12 articles were included for further analysis. The quality of these studies was evaluated according to the Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2) criteria. The Q test and heterogeneity I were used to evaluate the heterogeneity due to non-threshold effects, and Stata 15.0 was used for statistical analysis to evaluate the diagnostic value of the CVR cutoff value of 1.6 for fetal hydrops due to CLM.
RESULTS
A total of 12 studies were included. The QUADAS-2 indicated that the risk of bias was relatively low, and the clinical applicability was relatively high. Statistical analysis was performed on included studies using a random effect model. Meta-analysis showed that the pooled sensitivity, specificity, diagnostic ratio and summary receiver operating characteristic (SROC) for the diagnosis of fetal hydrops by CVR were 0.86 (95% CI, 0.72-0.93; I = 59.84), 0.90 (95% CI, 0.88-0.93; I = 31.94), 58 (95% CI, 22-149; I = 100%), 0.93 (95% CI, 0.91-0.95).
CONCLUSIONS
The sensitivity and specificity of CVR cut-off value 1.6 for the diagnosis of CLM-induced fetal hydrops were high, no publication bias was observed, and the CVR cut-off value 1.6 is meaningful for the early diagnosis prediction of CLM-induced fetal hydrops.
Topics: Cystic Adenomatoid Malformation of Lung, Congenital; Female; Humans; Hydrops Fetalis; Lung; Lung Diseases; Pregnancy; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 35658911
DOI: 10.1186/s13023-022-02347-0 -
Genetics in Medicine : Official Journal... Jan 2021Hydrops fetalis (HF), accumulation of fluid in two or more fetal compartments, is life-threatening to the fetus. Genetic etiologies include many chromosomal and...
Hydrops fetalis (HF), accumulation of fluid in two or more fetal compartments, is life-threatening to the fetus. Genetic etiologies include many chromosomal and monogenic disorders. Despite this, the clinical workup typically evaluates limited genetic targets. To support broader molecular testing of pregnancies with HF, we cataloged the spectrum of monogenic disorders associated with nonimmune hydrops fetalis (NIHF). We performed a systematic literature review under PROSPERO tag CRD42018099495 of cases reporting NIHF meeting strict phenotypic criteria and well-defined genetic diagnosis. We ranked the evidence per gene based on number of reported cases, phenotype, and molecular/biochemical diagnosis. We identified 131 genes with strong evidence for an association with NIHF and 46 genes with emerging evidence spanning the spectrum of multisystem syndromes, cardiac disorders, hematologic disorders, and metabolic disorders. Several genes previously implicated with NIHF did not have any reported cases in the literature with both fetal hydrops and molecular diagnosis. Many genes with strong evidence for association with NIHF would not be detected using current sequencing panels. Nonimmune HF has many possible monogenic etiologies, several with treatment implications, but current diagnostic approaches are not exhaustive. Studies are needed to assess if broad sequencing approaches like exome sequencing are useful in clinical management of HF.
Topics: Female; Fetus; Humans; Hydrops Fetalis; Pregnancy; Prenatal Care; Exome Sequencing
PubMed: 33082562
DOI: 10.1038/s41436-020-00967-0 -
American Journal of Medical Genetics.... May 2024RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or... (Meta-Analysis)
Meta-Analysis Review
RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies.
Topics: Pregnancy; Male; Female; Humans; Hydrops Fetalis; Exome Sequencing; Fathers
PubMed: 38156365
DOI: 10.1002/ajmg.a.63494 -
Prenatal Diagnosis Nov 2023Several factors associated with poor outcome in patients with prenatally diagnosed sacrococcygeal teratoma (SCT) have been found. However, the prognostic accuracy of... (Meta-Analysis)
Meta-Analysis Review
Several factors associated with poor outcome in patients with prenatally diagnosed sacrococcygeal teratoma (SCT) have been found. However, the prognostic accuracy of these factors has not been well established. Therefore, we aimed to systematically review the prognostic accuracy of factors associated with poor outcome in these patients. We queried Search Premier, COCHRANE Library, EMCARE, EMBASE, PubMed, ScienceDirect, and Web of Science databases to identify studies regarding patients with prenatally diagnosed SCT. Poor outcome was defined as termination of pregnancy (TOP), intrauterine fetal death (IUFD), or perinatal death. We estimated the odds ratio of factors associated with poor outcome. Eleven studies (447 patients) were included. Overall mortality, including TOP, was 34.9%. Factors associated with poor outcome in fetuses with prenatally diagnosed SCT were cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, and placentomegaly. A tumor volume to fetal weight ratio (TFR) of >0.12 before a gestational age of 24 weeks is predictive of poor outcome. The prognostic accuracy of factors associated with poor outcome in fetuses prenatally diagnosed with SCT seems promising. Factors associated with cardiac failure such as cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, placentomegaly, and TFR >0.12 were found to be predictive of poor outcome.
Topics: Pregnancy; Female; Humans; Infant; Prognosis; Hydrops Fetalis; Ultrasonography, Prenatal; Teratoma; Cardiomegaly; Sacrococcygeal Region
PubMed: 37964422
DOI: 10.1002/pd.6457 -
Hemoglobin Nov 2020Thalassemia is a genetic mutation of the α- or β-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies... (Meta-Analysis)
Meta-Analysis
Thalassemia is a genetic mutation of the α- or β-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies that investigated the clinical effectiveness of calcium channel blockers (CCBs) in conjunction with chelation therapy for reducing iron overload in patients with thalassemia. A systematic search was conducted in PubMed, Institute for Scientific Information (ISI) Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Virtual Health Library. Original studies reporting the use of CCBs in patients with thalassemia were included for meta-analysis. A total of five randomized studies including 210 patients were included with a follow-up period of 3-12 months. There was no significant difference between amlodipine and control groups in increasing the heart T2* magnetic resonance imaging (MRI) [mean difference (MD) 95% confidence interval (95% CI) = -1.9 (-4.4 to 0.5), = 0.119] or reducing the liver iron concentration [MD 95% CI = -0.046 (-0.325 to 0.2), = 0.746]. Although there were no serious adverse events reported in the included trials, further studies are recommended to strengthen our findings.
Topics: Amlodipine; Biomarkers; Calcium Channel Blockers; Chelation Therapy; Drug Therapy, Combination; Humans; Iron Chelating Agents; Iron Overload; Magnetic Resonance Imaging; Randomized Controlled Trials as Topic; Treatment Outcome; beta-Thalassemia
PubMed: 33430665
DOI: 10.1080/03630269.2020.1853561