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JPMA. the Journal of the Pakistan... Jan 2021To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening.
OBJECTIVE
To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening.
METHODS
The cross-sectional study was conducted at King Fahad Central Hospital, Jazan, Saudi Arabia, from January 2018 to May 2019, and comprised blood samples of individuals visiting the premarital screening clinic. The samples were analyzed for complete blood counts and haemoglobin electrophoresis. Molecular analysis of samples suspected for alpha thalassemia was done using alpha-globin StripAssay kit. Data was anlaysed using SPSS 20.
RESULTS
Of the 3,970 samples analysed, 1,859(46.83%) were from males and 2,111(53.17%) from females. The overall frequency of suspected alpha thalassemia was 4.43% based upon haematological parameters including complete blood count and haemoglobin electrophoresis. Overall, 80 suspected samples were selected for genetic analyses, and, of them, 76 (95%) were positive for deletional and non-deletional mutations of alpha-globin genes, while 4 (5%) were negative for any of the 21 mutations tested.
CONCLUSIONS
Alpha thalassemia was found to be highly prevalent in the study area.
Topics: Cross-Sectional Studies; Female; Genotype; Humans; Male; Saudi Arabia; alpha-Globins; alpha-Thalassemia
PubMed: 33484530
DOI: 10.47391/JPMA.864 -
Cold Spring Harbor Perspectives in... Mar 2017Recent genome sequencing efforts in a variety of cancers have revealed mutations and/or structural alterations in and , which together encode a complex that deposits... (Review)
Review
Recent genome sequencing efforts in a variety of cancers have revealed mutations and/or structural alterations in and , which together encode a complex that deposits histone variant H3.3 into repetitive heterochromatin. These regions include retrotransposons, pericentric heterochromatin, and telomeres, the latter of which show deregulation in /-mutant tumors. Interestingly, and mutations are often found in pediatric tumors, suggesting a particular developmental context in which these mutations drive disease. Here we review the functions of ATRX and DAXX in chromatin regulation as well as their potential contributions to tumorigenesis. We place emphasis on the chromatin remodeler ATRX, which is mutated in the developmental disorder for which it is named, α-thalassemia, mental retardation, X-linked syndrome, and at high frequency in a number of adult and pediatric tumors.
Topics: Adaptor Proteins, Signal Transducing; Adult; Animals; Child; Chromatin Assembly and Disassembly; Co-Repressor Proteins; Disease Models, Animal; Histones; Humans; Mental Retardation, X-Linked; Mice; Molecular Chaperones; Mutation; Neoplasms; Nuclear Proteins; Telomere; X-linked Nuclear Protein; alpha-Thalassemia
PubMed: 28062559
DOI: 10.1101/cshperspect.a026567 -
Saudi Medical Journal Nov 2015Alpha-thalassemia (α-thal) is a disorder caused by the deletion of single or double α-globin genes, and/or point mutations in the α-globin genes. There are 2 common... (Review)
Review
Alpha-thalassemia (α-thal) is a disorder caused by the deletion of single or double α-globin genes, and/or point mutations in the α-globin genes. There are 2 common types of α-globin genes; HBA2 and HBA1. Recently, it has been discovered that the HBA2 gene is replaced by a unique HBA12 gene convert in 5.7% of the Saudi population. The α-globin genes have been emerging as a molecular target for the treatment of β-thalassemia (β-thal). Hence, it is essential to understand the molecular nature of α-globin genes to treat the most prevalent hemoglobin disorders, such as sickle cell disease, α-thal, and β-thal prevalent in the Kingdom of Saudi Arabia. Thirty-two different α-globin genotypes have been observed in the Saudi population. This review outlines the classification of the α-globin genes on the basis of their molecular nature and complex combinations of α-globin genes, and their variants predominant in Saudis.
Topics: Chromosome Mapping; Humans; Saudi Arabia; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 26593158
DOI: 10.15537/smj.2015.11.12704 -
Reports of Biochemistry & Molecular... Oct 2021alpha-Thalassemia is caused primarily by deletions of one to two alpha-globin genes and is characterized by absent or deficient production of alpha-globin protein. The...
BACKGROUND
alpha-Thalassemia is caused primarily by deletions of one to two alpha-globin genes and is characterized by absent or deficient production of alpha-globin protein. The South-East Asia (SEA) deletion, 3.7-kb and 4.2-kb deletions are the most common causes. The present study aimed to observe the molecular characteristics of this common alpha-Thalassemia deletions and analyse its haematological parameter.
METHODS
Blood samples from 173 healthy volunteers from thalassemia carrier screening in Yogyakarta Special Region were used. Haematological parameters were analysed and used to predict the carrier subjects. Genotype of suspected carriers was determined using multiplex gap-polymerase chain reaction and its haematological parameters were compared. The boundary site of each deletion was determined by analysing the DNA sequences.
RESULTS
Seventeen (9.8%) of the volunteers were confirmed to have alpha-Thalassemia trait. Of these, four genotypes were identified namely -α/αα (58.8%), -α/αα (5.9%), -α/-α (5.9%) and - -/αα (29.4%). The 5' and 3' breakpoints of SEA deletion were located at nt165396 and nt184700 of chromosome 16, respectively. The breakpoint regions of 3.7-kb deletion were 176-bp long, whereas for 4.2-kb deletion were 321-bp long. The haematological comparison between normal and those with alpha-Thalassemia trait genotype indicated a significant difference in mean corpuscular volume (MCV) (p< 0.001) and mean corpuscular haemoglobin (MCH) (p< 0.001). As for identifying the number of defective genes, MCH parameter was more reliable (p= 0.003).
CONCLUSION
The resultant molecular and haematological features provide insight and direction for future thalassemia screening program in the region.
PubMed: 34981010
DOI: 10.52547/rbmb.10.3.346 -
Prenatal Diagnosis Jun 2023Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue...
OBJECTIVE
Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue edema, ascites, or hydrops. Many LAs are caused by single nucleotide variants, which are not detected on routine prenatal testing.
METHODS
Demographic data were compared between two subcohorts, those with clinically significant fetal edema (CSFE) and isolated fetal edema. A targeted variant analysis of LA genes was performed using American College of Medical Genetics criteria on whole exome sequencing (WES) data generated for 71 fetal edema cases who remained undiagnosed after standard workup.
RESULTS
CSFE cases had poor outcomes, including preterm delivery, demise, and maternal preeclampsia. Pathogenic and likely pathogenic variants were identified in 7% (5/71) of cases, including variants in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant. Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases. In CSFEs, VOUS were found in CELSR1, EPHB4, TIE1, PIEZO1, ITGA9, RASopathy genes, SOS1, SOS2, and RAF1.
CONCLUSIONS
WES identified pathogenic and likely pathogenic variants and VOUS in LA genes in 51% of fetal edema cases, supporting WES and expanded hydrops panels in cases of idiopathic fetal hydrops and fluid collections.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Hydrops Fetalis; Fetus; Lymphatic Abnormalities; Ion Channels; p120 GTPase Activating Protein
PubMed: 36959127
DOI: 10.1002/pd.6345 -
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 -
BioMed Research International 2019Unlike the other hemoglobinopathies, few researches have been published concerning -thalassemia in Morocco. The epidemiological features and the mutation spectrum of...
Unlike the other hemoglobinopathies, few researches have been published concerning -thalassemia in Morocco. The epidemiological features and the mutation spectrum of this disease are still unknown. This regional newborn screening is the first to study -thalassemia in the north of Morocco. During the period from January 2015 to December 2016, 1658 newborns umbilical blood samples were investigated. Suspected newborns were screened for -globin defects using Gap-PCR and Multiplex Ligation-dependent Probe Amplification technique. The prevalence of -thalassemia, its mutation spectrum, and its allelic frequencies were described for the first time in Morocco. Six different -globin genetic disorders were detected in 16 neonates. This screening valued the prevalence of -thalassemia in the studied population at 0.96% and showed the wide mutation spectrum and the heterogeneous geographical distribution of the disease. A high rate of carriers was observed in Laouamra, a rural commune in Larache province. Heterogeneity of -globin alleles in Morocco explains the high variability of -thalassemia severity. This diversity reflects the anthropological history of the country. These results would contribute to the prevention of thalassemia in Morocco directing the design of a nationwide screening strategy and awareness campaign.
Topics: Alleles; Female; Gene Frequency; Humans; Infant, Newborn; Male; Morocco; Mutation; Prevalence; alpha-Globins; alpha-Thalassemia
PubMed: 31001551
DOI: 10.1155/2019/2080352 -
International Journal of Molecular... Mar 2023Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original... (Review)
Review
Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major ("homozygous alpha-thalassemia-1") or hemoglobin Bart's disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart's hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart's hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart's hydrop fetalis.
Topics: Female; Pregnancy; Humans; alpha-Thalassemia; Hydrops Fetalis; Placenta; Hemoglobins, Abnormal; Extracellular Vesicles; Prenatal Diagnosis
PubMed: 36982732
DOI: 10.3390/ijms24065658 -
Clinical and Applied... 2022About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing... (Review)
Review
About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing methods would cause missed diagnosis of partial static thalassemia. Here, we reviewed and summarized a set of simple and clinically feasible thalassemia detection protocols adopted by the Prenatal Diagnosis and Reproductive Center of our hospital. From January 1, 2015, to December 31, 2020, 31 512 peripheral blood samples and 3828 prenatal samples were collected in our study. All the peripheral blood samples were performed through thalassemia screening by routine blood tests and hemoglobin electrophoresis and gene detection. The prenatal diagnosis would be implemented for the fetus if the parents were carriers of the same type of thalassemia. A total of 6137 (19.48%) cases were diagnosed as thalassemia, in which 4749 (15.07%) were α-thalassemia, 1196 (3.80%) were β-thalassemia and 192 (0.61%) were co-inheritance of α- and β-thalassemia. For prenatal samples, 3160 (82.55%) cases were diagnosed as thalassemia, in which 2021 (52.80%) were α-thalassemia, 997 (26.05%) were β-thalassemia and 142 (3.71%) were co-inheritance of α- and β-thalassemia. In addition, we also found five novel mutations, including NC_000016.9:g.223681-227492del3812; HBA1: c.301-31_301-24delCTCGGCCCinsG; HBA2: c.95+7C>T for α-thalassemia and HBB: c.263_276delCACTGAGTGAGCTG; HBB: c.315+143G>A for β-thalassemia. The present study updates the epidemiological characteristics and mutation spectrum of thalassemia in Southern China and demonstrated five novel mutations. Our research provides a reference for clinical diagnosis and treatment, prenatal diagnosis, or reproductive genetic counseling for patients with thalassemia in Guangdong.
Topics: China; Female; Genotype; Humans; Molecular Epidemiology; Mutation; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia; beta-Thalassemia
PubMed: 35979587
DOI: 10.1177/10760296221119807 -
American Journal of Hematology Jan 2018Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in... (Review)
Review
Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in inappropriate shrinkage or swelling of the erythrocytes, and water lost or gained osmotically. The last few years have been crucial for new acquisitions in this field in terms of identifying new causative genes and of studying their pathogenetic mechanisms. This review summarizes the main features of erythrocyte membrane transport diseases, dividing them into forms with either isolated erythroid phenotype (nonsyndromic) or extra-hematological manifestations (syndromic), and focusing particularly on the most recent advances regarding dehydrated forms of hereditary stomatocytosis and familial pseudohyperkalemia.
Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Congenital; Child; Humans; Hydrops Fetalis; Middle Aged; Young Adult
PubMed: 28971506
DOI: 10.1002/ajh.24929