Carrier Screening For Inherited Genetic Conditions
Vincenzo Berghella in Obstetric Evidence Based Guidelines, 2022
Alpha-thalassemia results from a gene deletion of two or more copies of the four alpha-globin genes on chromosome 16. It is common among individuals of Southeast Asian, African, West Indian, and Mediterranean ancestry. Deletion of two genes, alpha-thalassemia trait, causes a mild hemolytic anemia. The deletions may occur on the same chromosome (cis aa/-) or on two different chromosomes (trans a-/a-). Individuals of Southeast Asian descent are more likely to carry the cis configuration compared to their African counterparts. Individuals with alpha-thalassemia trait are at increased risk for having a child with a more severe form of alpha-thalassemia. Hemoglobin H disease is caused by the deletion of three alpha-globin genes. Affected individuals have mild to moderate hemolytic anemia. Alpha-thalassemia major (Hb Bart disease) results from the absence of functional alpha-globin genes. Fetal hydrops and intrauterine fetal demise is the expected outcome in these cases due to the inability to produce functional HbF. Hemoglobin Bart disease does not usually occur in fetuses of alpha-thalassemia carriers of African origin, since individuals of African descent usually have the trans-configuration genotype. See Chap. 14 in Maternal-Fetal Medicine Evidence Based Guidelines.
The Red Blood Cell In Thalassemia *
Ronald L. Nagel in Genetically Abnormal Red Cells, 2019
The α-thalassemias are usually characterized by partial or complete deficiency or a-globin chains. Normally there are four a-globin genes per diploid genome, located on the short arm of chromosome 16. The two α genes on each chromosome are arranged in tandem, adjacent to each other. In a nonthalassemic individual the four genes are expressed at an approximately equal rate. α-Thalassemia may result from a deletion or malfunction of one, two, three, or all four genes. Deletion or dysfunction of a single gene is essentially asymptomatic. In the absence of two genes the condition is known as α-thalassemia trait. Patients with hemoglobin H disease have only one functioning α gene, and produce about 25% of the α chains. Deletion or mutations in all four genes is lethal and results in a condition known as hydrops fetalis. Molecular analysis revealed that in most cases α-thalassemia results from deletion of either one or both tandemly located α genes.16,18 The extent of the deletions and their end points vary, and they may encompass the entire α gene cluster, including the two embryonic ζ genes. There are also nondeletion α-thalassemias, caused by point mutations, usually in one of the two neighboring α genes. A case with identical point mutations on the two adjacent genes (situated in cis on the same chromosome) has been recently described.19 As suggested by the authors, this finding may reflect a recent gene conversion event within the human α-globin locus.
Hematological problems in the neonate
Prem Puri in Newborn Surgery, 2017
If the anemia is due to a hemolytic process, then jaundice is almost always present. When the hemolytic process is secondary to a red cell membrane defect, the abnormally shaped red blood cells are removed from the peripheral circulation, and the jaundice is usually accompanied by mild to moderate splenomegaly. Jaundice is also frequently seen in neonates with inherited red cell enzyme deficiencies, which can cause significant damage to the erythrocytes. Most of the hemoglobinopathies, apart from alpha-thalassemia major and hemoglobin-H (HbH) disease, do not cause neonatal jaundice.43
Successful four-factor preimplantation genetic testing: α- and β-thalassemia, human leukocyte antigen typing, and aneuploidy screening
Published in Systems Biology in Reproductive Medicine, 2021
Dongjia Chen, Xiaoting Shen, Yan Xu, Chenhui Ding, Qingjian Ye, Yiping Zhong, Yanwen Xu, Canquan Zhou
Patients with dual β-thalassemia mutations have β-thalassemia major and often cannot survive to child-bearing age. Patients with two types of α-thalassemia mutations, however, can experience mild-to-moderate anemia or hemoglobin H (HbH) disease, thereby having a longer life expectancy and reproductive capability than those with dual β-thalassemia mutations. When couples are carriers of α- and β-double thalassemia with a single α-thalassemia mutation, such as these three families, the probability of achieving a transferable embryo is 0.75 × 0.75 = 56.25%. In our study, the probability was close to the theoretical value at 51.5% (17/33). However, if one partner of each couple was HbH or carried two types of α-thalassemia mutations, the probability would decrease to 0.5 × 0.75 = 37.5%. Certainly, the probability would reduce by a quarter when combined with HLA typing, further declining when combined with PGT-A. For example, when combining PGT for two types of thalassemia and aneuploidy screening, Family 2 achieved no transferable embryo. To provide a large number of embryos for biopsy, poor responders generally need to undergo several ovarian stimulation cycles. If no blastocyst with matched HLA is obtained, patients may choose to transfer unaffected euploid embryos or reenter new PGT cycles.
Epidemiologic study of major complications in adolescent and adult patients with thalassemia in Northeastern Thailand: the E-SAAN study phase I
Published in Hematology, 2018
Nattiya Teawtrakul, Arunee Jetsrisuparb, Saranya Pongudom, Chittima Sirijerachai, Kanchana Chansung, Chinadol Wanitpongpun, Supan Fucharoen
Genotype group classification including; β-thalassemia/hemoglobin E defined as the presence of β-gene mutation(s) and hemoglobin E by hemoglobin type testing and or the DNA analysis.Combined α and β-thalassemia defined as the group of patients with Hb H disease, compound heterozygous Hb H and heterozygous Hb E (EABart’s disease), compound heterozygous Hb H and homozygous Hb E (EFBart’s disease), compound heterozygous Hb H with Hb CS and heterozygous Hb E (EABart’s disease with Hb CS), compound heterozygous Hb H with Hb CS and homozygous Hb E (EFBart’s disease with Hb CS), compound heterozygous Hb H with Hb Pakséand heterozygous Hb E (EABart’s disease with Hb Paksé).α-thalassemia defined as the group of patients with hemoglobin H (Hb H) disease with hemoglobin Constant Spring (Hb CS), Hb H disease with hemoglobin Paksé (Hb Paksé).
Clinical and genetic characteristics of hemoglobin H disease in Iran
Published in Pediatric Hematology and Oncology, 2022
Hassan Abolghasemi, Sharareh Kamfar, Azita Azarkeivan, Mehran Karimi, Bijan Keikhaei, Fahimeh Abolghasemi, Mohammad H. Radfar, Peyman Eshghi, Samin Alavi
The hemoglobin (Hb) molecule is a tetrameric protein including two alpha and two beta subunits that are synthesized independently by 2 multigene clusters located on chromosome 16 and 11 respectively.1 Thalassemic mutations in globin genes lead to the reduced or absent synthesis of hemoglobin chains.2 Alpha-thalassemia (α) as one of the most prevalent monogenic diseases in the world especially in Southeast Asia and the Middle East,3,4 is characterized by changes in the level of α-globin gene expression due to deletions or point mutations in one or more alpha globin genes.5–7 On the other hand, according to the frequency of missed or nonfunctional α-globin genes, α thalassemia can be classified to silent alpha thalassemia (single α-gene deletion (-α/αα)), alpha thalassemia trait (two alpha gene deletions in cis (–/αα) or in trans (- α/- α)), hemoglobin H disease (Hb H) (mutations in three α-globin genes (–/-α or –/αTα) and Hb Bart’s hydrops fetalis (deletion of four α-genes (- -/- -)).8,9
Related Knowledge Centers
- Gene Expression
- Hemoglobin A
- Genotype
- Hemoglobin
- Red Blood Cell
- Alpha-Thalassemia
- Deletion
- Hemoglobin Subunit Alpha
- Hemoglobin, Alpha 2
- Nucleic Acid Sequence