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Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2022β-thalassemia (β-thal) is one of the most common genetic diseases in the world, its pathogenesis is extremely complex and there is no effective treatment at present....
β-thalassemia (β-thal) is one of the most common genetic diseases in the world, its pathogenesis is extremely complex and there is no effective treatment at present. The birth of children with moderate and severe β-thal brings economic pressure to families, social medical and health services. Long noncoding RNA (lncRNA) is a type of noncoding protein transcripts with a length greater than 200 nucleotides, which is involved in a variety of biological processes, such as cell proliferation, differentiation and chromosome variation and plays an important role in the epigenetic and post-transcriptional regulation of genes. It has potential value in the diagnosis, prevention and treatment of β-thal. LncRNA possesses the characteristics such as tissue specificity, cell specificity, developmental stage specificity, space-time specificity and disease specificity, and its complex interaction network has become a challenge to translate research results into clinical practice. Taking lncRNA as an entry point, in-depth understanding of the function of lncRNA in β-thal and explanation of its related regulatory mechanisms will provide theoretical basis for targeting treatment of β-thal, which can improve the diagnosis and treatment of β-thal.
Topics: Cell Differentiation; Child; Gene Expression Regulation; Humans; RNA, Long Noncoding; beta-Thalassemia
PubMed: 35545416
DOI: 10.11817/j.issn.1672-7347.2022.210411 -
BMC Nephrology Dec 2021Beta(β)-thalassemia is one of the most common hereditary hematologic disorders. Patients with thalassemia minor (TM) are often asymptomatic and the rate of renal...
OBJECTIVE
Beta(β)-thalassemia is one of the most common hereditary hematologic disorders. Patients with thalassemia minor (TM) are often asymptomatic and the rate of renal dysfunction is unknown in these patients. Due to the high prevalence of renal dysfunction in Iran, the current study aimed to determine renal tubular dysfunction in patients with beta-TM.
METHODS
In this case-control study, 40 patients with TM and 20 healthy subjects were enrolled and urinary and blood biochemical analysis was done on their samples. Renal tubular function indices were determined and compared in both groups. Data was analyzed by SPSS software, version 20.0.
RESULTS
The fraction excretion (FE) of uric acid was 8.31 ± 3.98% in the case and 6.2 ± 34.71% in the control group (p = 0.048). Also, FE of potassium was significantly higher in patients with TM (3.22 ± 3.13 vs. 1.91 ± 0.81; p = 0.036). The mean Plasma NGAL level was 133.78 ± 120.28 ng/mL in patients with thalassemia and 84.55 ± 45.50 ng/mL in the control group (p = 0.083). At least one parameter of tubular dysfunction was found in 45% of patients with thalassemia.
CONCLUSION
Based on the results of this study, the prevalence of tubular dysfunction in beta-thalassemia minor patients is high. Due to the lack of knowledge of patients about this disorder, periodic evaluation of renal function in TM patients can prevent renal failure by early diagnosis.
Topics: Adult; Case-Control Studies; Female; Humans; Kidney Tubules; Male; Middle Aged; beta-Thalassemia
PubMed: 34872508
DOI: 10.1186/s12882-021-02602-9 -
BMC Medical Genetics May 2020Beta (β)-thalassemia is one of the most common inherited disorders worldwide, with high prevalence in the Mediterranean, the Middle East and South Asia. Over the past...
BACKGROUND
Beta (β)-thalassemia is one of the most common inherited disorders worldwide, with high prevalence in the Mediterranean, the Middle East and South Asia. Over the past 40 years, awareness and prevention campaigns in many countries have greatly reduced the incidence of affected child births. In contrast, much remains to be done in South-Asia. Thus, for Pakistan, an estimated ~ 7000 children annually are born with thalassemia, with no sign of improvement. Although there is good agreement that intermarriage of carriers significantly contributes to the high prevalence of the disorder, effective tools for molecular screening and diagnosis on which to base prevention programs are not readily available.
METHODS
Here, we present results for a novel LeanSequencing™ process to identify a combination of 18 β-thalassemia mutations (including the sickle cell anemia mutation, HbS, and structural variants HbC and HbE) and 2 hemochromatosis mutations in a multi-ethnic population of 274 pediatric and adolescent patients treated at Afzaal Memorial Thalassemia Foundation in Karachi, Pakistan.
RESULTS
We found substantial differences in the predominance of disease-causing mutations among the principal ethnic groups in our cohort. We also found the hemochromatosis mutation H63D C > G in 61 (or 22.1%) of our patients including 6 (or 2.2%) homozygotes.
CONCLUSIONS
To our knowledge, this is the first screen combining a large set of β-thalassemia and hemochromatosis mutations, so as to facilitate the early identification of patients who may be at increased potential risk for complications from iron overload and thereby to improve the prospective management of thalassemia patients.
Topics: Adolescent; Adult; Alleles; Child; Child, Preschool; DNA Mutational Analysis; Disease Management; Female; Genetic Predisposition to Disease; Genotype; Hemochromatosis; Hemoglobins, Abnormal; Humans; Infant; Male; Mutation; Young Adult; beta-Thalassemia
PubMed: 32414341
DOI: 10.1186/s12881-020-01017-x -
Frontiers in Endocrinology 2022Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are... (Review)
Review
Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.
Topics: Humans; Male; Female; Fertility Preservation; beta-Thalassemia; Quality of Life; Semen; Counseling; Anemia, Sickle Cell; Ovarian Hyperstimulation Syndrome
PubMed: 36353243
DOI: 10.3389/fendo.2022.985525 -
Acta Bio-medica : Atenei Parmensis Aug 2023Beta thalassemia major (β-TM) is a genetic blood disorder requiring lifelong blood transfusions. The resulting iron overload damages multiple organs, particularly the...
Beta thalassemia major (β-TM) is a genetic blood disorder requiring lifelong blood transfusions. The resulting iron overload damages multiple organs, particularly the heart and endocrine organs. This study aimed to describe and assess the predictors of survival and complications in Omani patients with β-TM. Methods: All β-TM patients registered in the day care of Sultan Qaboos University Hospital were included in this retrospective study. Results: There were 187 patients with β-TM with a median follow-up of 24.9 years. The median ages at diagnosis and the start of chelation were 0.7 and 4.8 years, respectively. The following complications developed at different time points [Median (age in years), Complication Free Probability at 20 years]: Death (20.0 years;85%), hypogonadism (15.9 years;50%), insulin-dependent or non-insulin dependent diabetes (20.0 years;88%), cardiac complications (20.3 years;91%), osteoporosis (20.7 years;96%), hypothyroidism (25.7 years;97%), liver complications (7.3 years;54%). The number of complications predicted death (P = 0.0038). Those born after 1980 had a lower risk of death (P = 0.005), hypogonadism (P = < 0.0001), and cardiac complications (P = 0.004). Higher serum ferritin at the start of chelation was associated with the development of diabetes (P = < 0. 001). Conclusions: This long-term study shows complications development at different ages, and the number of complications is associated with survival. Later birth cohorts had a lower risk of death, hypogonadism, and cardiac complications. There was a persistent negative impact of delay in the start of iron chelation that is present even after a long follow-up. (www.actabiomedica.it).
Topics: Humans; Follow-Up Studies; beta-Thalassemia; Retrospective Studies; Iron Overload; Hypogonadism
PubMed: 37539594
DOI: 10.23750/abm.v94i5.14856 -
Scientific Reports Mar 2022Increased HbA levels are the characteristic feature of β-thalassemia carriers. A subset of carriers however do not show HbA levels in the typical carrier range...
Increased HbA levels are the characteristic feature of β-thalassemia carriers. A subset of carriers however do not show HbA levels in the typical carrier range (≥ 4.0%) but show borderline HbA levels. As a result, these carriers escape diagnosis and carry the risk of having β-thalassemia major offspring. Borderline HbA values may occur as a consequence of mild β-thalassemia mutations, co-inherited β-thalassemia and α- or δ- thalassemia or iron deficiency anemia. However, there is insufficient knowledge regarding the cause of borderline HbA levels in specific populations. This study aimed to identify the determinants of borderline HbA levels (which we have considered as HbA 3.0-3.9%) in 205 individuals. Primary screening involved detecting the presence of iron deficiency anemia followed by molecular analysis of α, β and δ globin genes. Remarkably, 168 of 205 individuals were positive for a defect. 87% (149/168) of positive individuals were heterozygous for β thalassemia with (59/149) or without (90/149) the presence of co-existing IDA, α or δ gene defects. Notably, 20 of 149 β thalassemia carriers showed HbA < 3.5% and MCV > 80fL. 7 of these 20 carriers were married to carriers of hemoglobinopathies. Our findings describe the genetic basis of borderline HbA levels and emphasize the necessity of a molecular diagnosis in these individuals in the routine clinical setting.
Topics: Hemoglobinopathies; Heterozygote; Humans; Mass Screening; Mutation; beta-Thalassemia
PubMed: 35354866
DOI: 10.1038/s41598-022-09250-5 -
Molecular Genetics & Genomic Medicine Aug 2022β-thalassemia syndromes are the most common hereditary blood disorders in the world and are recognized as a major health problem in Morocco. They are characterized by...
BACKGROUND
β-thalassemia syndromes are the most common hereditary blood disorders in the world and are recognized as a major health problem in Morocco. They are characterized by the reduction or the absence of β-globin chain synthesis. The severity of the disease depends on the nature of the variants affecting the β-globin gene (HBB), and each ethnic group has its own mutation spectrum. Hereby, we present, for the first time, the molecular profile of β-thalassemia in the Eastern region of Morocco.
METHODS
This study concerns 39 cases from 33 families who were enrolled in the BRO Biobank. Nineteen were diagnosed with β-thalassemia major and 20 with β-thalassemia minor. To detect mutations of the β-globin gene, we have used RFLP-PCR and Sanger sequencing.
RESULTS
Nine known β-thalassemia variants have been identified. Among these, we reported, for the first time in the Moroccan population, the Czechoslovakian variant C38/39(-C) at homozygous state. The C39(C > T) was the most frequent variant (72.54%), followed by FSC5(-CT) (5.88%), FSC6(-A), IVS-1-110(G > A), -29(A > G), C38/39(-C) (3.92% each), and finally by IVS-I-1(G > A), IVS-II-1(G > A), and -56(G > C) (1.96%). Of particular interest this mutational spectrum of β-thalassemia is very different from that found in previous studies in Morocco or in other North African countries.
CONCLUSION
This study is the first contribution to the description of the molecular profile of β-thalassemia in the Eastern region of Morocco. It shows the high molecular heterogeneity of β-thalassemia in our country. Therefore, these results can be valuable for the implementation of carrier screening, genetic counseling, and prenatal diagnosis programs.
Topics: Humans; Morocco; Mutation; Polymorphism, Restriction Fragment Length; beta-Globins; beta-Thalassemia
PubMed: 35615994
DOI: 10.1002/mgg3.1970 -
Indian Pediatrics Jul 2021b-Thalassemia is one of the most prevalent monogenic diseases usually caused by quantitative defects in the production of b-globin, a component of adult hemoglobin...
b-Thalassemia is one of the most prevalent monogenic diseases usually caused by quantitative defects in the production of b-globin, a component of adult hemoglobin (a2b2), leading to severe anemia. Technological advances in genome sequencing, stem cell selection, viral vector development, transduction and gene-editing strategies now allow for efficient ex-vivo genetic manipulation of human hematopoietic stem cells that can lead to a meaningful clinical benefit in thalassemia patients. In this perspective, the status of the gene-therapy approaches available for transfusion-dependent thalassemia and early results of clinical trials are discussed. It is highly anticipated that gene therapies will soon become a treatment option for patients lacking compatible donors for hematopoietic stem cell transplant and will offer a suitable alternative for definitive treatment of b-thalassemia, even in young children.
Topics: Child, Preschool; Genetic Therapy; Genetic Vectors; Hemoglobins; Humans; Thalassemia; beta-Thalassemia
PubMed: 33772535
DOI: No ID Found -
Blood Jun 2015The thalassemias, together with sickle cell anemia and its variants, are the world's most common form of inherited anemia, and in economically undeveloped countries,... (Review)
Review
The thalassemias, together with sickle cell anemia and its variants, are the world's most common form of inherited anemia, and in economically undeveloped countries, they still account for tens of thousands of premature deaths every year. In developed countries, treatment of thalassemia is also still far from ideal, requiring lifelong transfusion or allogeneic bone marrow transplantation. Clinical and molecular genetic studies over the course of the last 50 years have demonstrated how coinheritance of modifier genes, which alter the balance of α-like and β-like globin gene expression, may transform severe, transfusion-dependent thalassemia into relatively mild forms of anemia. Most attention has been paid to pathways that increase γ-globin expression, and hence the production of fetal hemoglobin. Here we review the evidence that reduction of α-globin expression may provide an equally plausible approach to ameliorating clinically severe forms of β-thalassemia, and in particular, the very common subgroup of patients with hemoglobin E β-thalassemia that makes up approximately half of all patients born each year with severe β-thalassemia.
Topics: Animals; Down-Regulation; Genetic Therapy; Humans; Molecular Targeted Therapy; RNA Interference; RNA, Small Interfering; alpha-Globins; beta-Thalassemia
PubMed: 25869286
DOI: 10.1182/blood-2015-03-633594 -
Acta Haematologica 2022Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the... (Review)
Review
BACKGROUND
Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in hemoglobin E (HbE) beta thalassemia, the most common form of severe beta-thalassemia worldwide, have not previously been reported.
METHODS
We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the 2 largest treatment centers in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia.
RESULTS
Of a total of 255 actively registered patients with HbE thalassemia in the 2 centers, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady-state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting, and skin grafting.
CONCLUSION
Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.
Topics: Hemoglobin E; Humans; Leg Ulcer; Thalassemia; Wound Healing; beta-Thalassemia
PubMed: 34753145
DOI: 10.1159/000520731