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Frontiers in Endocrinology 2023To improve the accuracy of preimplantation genetic testing (PGT) in deletional α-thalassemia patients.
OBJECTIVE
To improve the accuracy of preimplantation genetic testing (PGT) in deletional α-thalassemia patients.
DESIGN
Article.
PATIENTS
fifty-two deletional α-thalassemia couples.
INTERVENTIONS
Whole genome amplification (WGA), Next-generation sequencing (NGS) and PCR mutation loci detection.
MAIN OUTCOME MEASURES
WGA, Single nucleotide polymorphism (SNP) and PCR mutation loci detection results; Analysis of embryo chromosome copy number variation (CNV).
RESULTS
Multiple Displacement Amplification (MDA) and Multiple Annealing and Looping-Based Amplification Cycles (MALBAC) methods for PGT for deletional α-thalassemia. Blastocyst biopsy samples (n = 253) were obtained from 52 deletional α-thalassemia couples. The results of the comparison of experimental data between groups MALBAC and MDA are as follows: (i) The average allele drop-out (ADO) rate, MALBAC MDA = 2.27% ± 3.57% 0.97% ± 1.4%, =0.451); (ii) WGA success rate, MALBAC MDA = 98.61% 98.89%, =0.851; (iii) SNP haplotype success rate, MALBAC MDA = 94.44% 96.68%, =0.409; (iv) The result of SNP haplotype analysis is consistent with that of Gap-PCR/Sanger sequencing results, MALBAC MDA = 36(36/72, 50%) 151(151/181, 83.43%), =0; (v) Valid SNP loci, MALBAC MDA = 30 ± 9 34 ± 10, =0.02; (vi) The mean CV values, MALBAC MDA = 0.12 ± 0.263 0.09 ± 0.40, =0.916; (vii) The average number of raw reads, MALBAC MDA =3244259 ± 999124 3713146 ± 1028721, =0; (viii) The coverage of genome (%), MALBAC MDA = 5.02 ± 1.09 5.55 ± 1.49, =0.008.
CONCLUSIONS
Our findings indicate that MDA is superior to MALBAC for PGT of deletional α-thalassemia. Furthermore, SNP haplotype analysis combined with PCR loci detection can improve the accuracy and detection rate of deletional α-thalassemia.
Topics: Pregnancy; Female; Humans; Preimplantation Diagnosis; alpha-Thalassemia; DNA Copy Number Variations; Genetic Testing; Alleles
PubMed: 38523870
DOI: 10.3389/fendo.2023.1176063 -
BMC Pregnancy and Childbirth Mar 2024Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have...
BACKGROUND
Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma.
CASE PRESENTATION
A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion.
CONCLUSION
Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Adult; Ritodrine; Hydrops Fetalis; Cesarean Section; Placenta; Obstetric Labor, Premature; Hemangioma; Syndrome
PubMed: 38509456
DOI: 10.1186/s12884-024-06391-5 -
Scientific Reports Mar 2024Abnormal hemoglobin anti-Lepore Hong Kong is a rare βδ fusion variants resulting from non-homologous crossover during meiosis. Anti-Lepore Hong Kong is known to...
Abnormal hemoglobin anti-Lepore Hong Kong is a rare βδ fusion variants resulting from non-homologous crossover during meiosis. Anti-Lepore Hong Kong is known to consistently exhibit significantly increased level of HbA2. In this study, we used multiplex ligation-dependent probe amplification (MLPA) and single molecular real-time (SMRT) sequencing, as well as Sanger sequencing, to identify variants in five unrelated families with abnormal elevated HbA2 level. All probands in these five families were found to be heterozygous for anti-Lepore Hong Kong. Among them, two families showed co-occurrence of β-thalassemia and α-thalassemia (-/ or αα/). Heterozygotes for anti-Lepore Hong Kong displayed an average HbA2 level of 17.7% and behaved normal. However, when combined with β-thalassemia and α-thalassemia, the probands exhibited higher HbA2 level (30.2-40.8%) and behaved with β-thalassemia trait. Furthermore, determination of the α/β-mRNA ratio revealed a slight downregulation of β-globin, similar to that of β-thalassemia minor. Our study is the first to identify compound heterozygotes for anti-Lepore Hong Kong, β-thalassemia and α-thalassemia, provide valuable information for prenatal counseling.
Topics: Humans; Pregnancy; Female; alpha-Thalassemia; Hemoglobins, Abnormal; beta-Thalassemia; beta-Globins
PubMed: 38509195
DOI: 10.1038/s41598-024-56921-6 -
Journal of Clinical Laboratory Analysis Mar 2024Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have...
BACKGROUND
Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have investigated the molecular characterization of α- and β-thalassemia in children from Guizhou, China.
METHODS
Between January 2019 and December 2022, a total of 3301 children, aged 6 months to 18 years, suspected of having thalassemia underwent molecular analysis.
RESULTS
Out of the total sample, 824 (25%) children were found to carry thalassemia mutations. The carrier rates of α-thalassemia, β-thalassemia, and α + β-thalassemia were determined as 8.1%, 15.6%, and 1.3%, respectively. Approximately 96.5% of the α-thalassemia gene mutations were --SEA (51%), αα (20.9%), -α (19.6%), and -α (5.0%). The most prevalent mutations of β-thalassemia were β (41.5%), β (37.7%), and β (11.3%). Additionally, we identified rare cases, including one case with αα/αα, two cases with triplicated α-thalassemia (one case with ααα/ααα and β/β and the other with ααα/αα and βE /β), and also one case with α α/-α and β/β.
CONCLUSIONS
Our study findings provide important insights into the heterogeneity of thalassemia carrier rates and molecular profiles among children in the Guizhou region. The findings support the development of prevention strategies to reduce the incidence of severe thalassemia in the future.
Topics: Child; Humans; Adolescent; beta-Thalassemia; alpha-Thalassemia; Genotype; China; Mutation
PubMed: 38506255
DOI: 10.1002/jcla.25022 -
Haematologica Mar 2024Hemoglobinopathies including thalassemias are among the most frequent genetic disorders worldwide. Primarily, these entities result from germline variants in the globin...
Hemoglobinopathies including thalassemias are among the most frequent genetic disorders worldwide. Primarily, these entities result from germline variants in the globin gene clusters and their cis-acting regulatory elements, and thus the WHO classifies thalassemias as inherited diseases. Non-inherited disorders of globin chain synthesis mimicking the phenotype of thalassemias have also been described and are referred to as acquired thalassemias. These forms mainly affect the alpha-globin genes and are observed at much lower frequencies...
PubMed: 38497167
DOI: 10.3324/haematol.2024.285083 -
Taiwanese Journal of Obstetrics &... Mar 2024Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as... (Review)
Review
Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of syndromic and single gene disorders associated with fetal pleural effusion that is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.
Topics: Pregnancy; Female; Humans; Noonan Syndrome; Pleural Effusion; Prenatal Diagnosis; Hydrops Fetalis; Lymphatic Abnormalities; Lymphatic Vessels
PubMed: 38485311
DOI: 10.1016/j.tjog.2024.01.011 -
Taiwanese Journal of Obstetrics &... Mar 2024Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as... (Review)
Review
Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides a comprehensive view of specific and non-specific chromosome aberrations associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.
Topics: Pregnancy; Female; Humans; Chromosome Aberrations; Pleural Effusion; Hydrops Fetalis; Prenatal Diagnosis; Heart Defects, Congenital; Ultrasonography, Prenatal
PubMed: 38485310
DOI: 10.1016/j.tjog.2024.01.010 -
Taiwanese Journal of Obstetrics &... Mar 2024Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as... (Review)
Review
Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of chromosomal abnormalities associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.
Topics: Pregnancy; Female; Humans; Pleural Effusion; Chromosome Aberrations; Hydrops Fetalis; Prenatal Diagnosis; Heart Defects, Congenital
PubMed: 38485309
DOI: 10.1016/j.tjog.2024.01.009 -
PeerJ 2024Homozygous α-thalassemia (SEA deletion) or Hb Bart's hydrops fetalis syndrome is a significant public health issue in Thailand and Southeast Asia. A prevention and...
Retrospective study and implementation of a low-cost LAMP-turbidimetric assay for screening α-thalassemia (SEA deletion): preventing and controlling Hb Bart's hydrops fetalis syndrome in Thailand.
Homozygous α-thalassemia (SEA deletion) or Hb Bart's hydrops fetalis syndrome is a significant public health issue in Thailand and Southeast Asia. A prevention and control program has been implemented in this region. This study focuses on retrospective laboratory data collected between January 2021 and April 2023 at a single center. Additionally, we developed a low-cost LAMP-turbidimetric assay to propose in the screening strategy. A total of 3,623 samples underwent screening tests (MCV, MCH, and DCIP), including 1,658 couple screenings (84.25%) and 310 single pregnant screenings (15.75%). Negative screenings, which did not require further investigation, were found in 75.51% for couple screenings and 46.58% for single pregnant screenings. At hemoglobin (Hb) analysis identified 129 couples which had fetuses at risk of severe thalassemia, whereas molecular analysis during the retrospective period revealed 210 samples with different genotypes. These remaining samples were validated using the low-cost LAMP-turbidimetric assay to detect α-thalassemia (SEA deletion). The developed LAMP turbidimetric assay demonstrated a sensitivity and specificity of 100% (36/36 × 100) and 97.7% (170/174 × 100), respectively, when compared with gap-PCR. Furthermore, we propose a strategy involving the addition of the low-cost LAMP-turbidimetric assay before performing the gold standard. This strategy represents a cost-saving of USD 2,608 based on 210 samples that required DNA analysis. Finally, the developed LAMP turbidimetric assays offer advantages such as reduced time, workload, cost savings, no need for highly developed instruments, and a straightforward interpreting process. Therefore, implementation of LAMP assays into routine settings would be improve the efficiency of prevention and control program for severe thalassemia disease in this region.
Topics: Female; Pregnancy; Humans; Retrospective Studies; Thailand; Hydrops Fetalis; alpha-Thalassemia; Cost Savings
PubMed: 38436007
DOI: 10.7717/peerj.17054 -
Circulation Research Mar 2024The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is... (Review)
Review
The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after mechanosensitive excitatory channels involved in touch and proprioception in mammals. However, more and more pieces of evidence point to the importance of PIEZO channels in cardiovascular activities and disease development. PIEZO channel-related cardiac functions include transducing hemodynamic forces in endothelial and vascular cells, red blood cell homeostasis, platelet aggregation, and arterial blood pressure regulation, among others. PIEZO channels contribute to pathological conditions including cardiac hypertrophy and pulmonary hypertension and congenital syndromes such as generalized lymphatic dysplasia and xerocytosis. In this review, we highlight recent advances in understanding the role of PIEZO channels in cardiovascular functions and diseases. Achievements in this quickly expanding field should open a new road for efficient control of PIEZO-related diseases in cardiovascular functions.
Topics: Animals; Female; Humans; Blood Pressure; Anemia, Hemolytic, Congenital; Biophysics; Hydrops Fetalis; Hypertension, Pulmonary; Mammals
PubMed: 38422173
DOI: 10.1161/CIRCRESAHA.123.322798