ALPHA THALASSEMIA

GENETIC DIAGNOSIS BEFORE EMBRYO TRANSFER ELIMINATES CONGENITAL HEMOLYTIC DISEASE

 1. Overview of Alpha thalassemia (α-thalassemia)

Thalassemia (also called congenital hemolytic disease) is a disease with a high incidence in children in Vietnam. With primary manifestations of anemia and iron overload, patients with thalassemia need to receive blood transfusions and receive lifelong chelation. People with congenital hemolytic disease will have a reduced ability to work and live, causing burden for families and the community. The cause of the disease is a mutation that causes a loss of gene coding for the α-globin and β-globin chains that cause alpha thalassemia and beta-thalassemia, respectively. The gene region of alpha thalassemia disease is located on short wing chromosome 16 (16p13.3) including 2 genes: HbA1 and HbA2, which encode for alpha-1 globin and alpha-2 globin chains, respectively (Figure 1) [1, 3 ]. Alpha thalassemia is the most common inherited hemoglobin (Hb) genetic disorder in the world, with gene frequencies ranging from 1% to 98% in the tropics and subtropics. In which the dominant mutant over 95% of α-thalassemia disease is recognized in relation to the loss of one or both α-globin genes on chromosome 16. The most common of these is the -α segment loss. and -α.4.2, two mutagenic mutations common in Southeast Asia (–SEA) and the Mediterranean (–FIL) [1]. Losing the SEA segment causes the loss of the DNA fragment containing both HBA1 and HBA2 genes about 20 kb long to cause α0-thal. The point mutation is less common but the most common is the HbCs (TAA-CAA) point mutation (accounting for up to 5% of the population in some parts of Southeast Asia). This mutation altered the ending trilogy of exon 3 on the alpha-2 globin gene, causing the synthesis of Constant Spring globin chain of 172 amino acids instead of the alpha-2 globin chain of 141 amino acids. The combination of SEA fragmentation and HbCs (–SEA / αCSα) forms HbH disease. Alpha thalassemia is mainly caused by a combination of two missing mutations, less association between point mutations and a point mutation [2, 4].

Hình 1: Diagram of the α-globin gene cluster. The genes are shown by a box. The scale is calculated in kilobases (kb). The most common α-thalassemia (α-thal) segment is represented as the gray bars and is divided into α + -thal and α0-thal [1].

2. Preliminary diagnosis of embryo transfer

PGT-M (Preimplantation genetic testing for monogenic disorders) is a technique to diagnose single-genome pre-embryonic disorders so that couples can have healthy and unborn babies. from parents. By amplifying the STR markers associated with the alpha globin gene, the parents can detect mutant-carrying alleles and screen for disease-free embryos. Genetic screening before embryo transfer is a very useful solution for couples to help reduce the burden on the family and society.

3. Prenatal diagnosis

Prenatal diagnosis is conducted with the following steps:

  • DNA testing of parents, mutation analysis of each person.
  • Amniocentesis or thoracic biopsy during pregnancy.
  • DNA testing of amniotic fluid or placenta.
  • Counseling on pregnancy termination if the fetus is seriously ill.
  • Use of pregnancy suspension (Obstetrics).

With the above prenatal diagnostic methods as above, many countries have achieved very good results, even prevented, not giving birth to children with severe congenital hemolytic disease. This not only limits the difficulties of families with patients, but also gathers resources to treat other congenital hemolytic patients well [5].

References:s

  1. Chong, S.S., et al., Single-tube multiplex-PCR screen for common deletional determinants of α-thalassemia. 2000. 95(1): p. 360-362.
  2. Derry, S., et al., Hematologic and biosynthetic studies in homozygous hemoglobin Constant Spring. 1984. 73(6): p. 1673-1682.
  3. Farashi, S., C.L.J.B.C. Harteveld, Molecules, and Diseases, Molecular basis of α-thalassemia. 2018. 70: p. 43-53.
  4. Suong N.T.B, Technique for genetic disease diagnosis. Medical Publishing House, 2013: p. 103-106.
  5. https://www.vinmec.com/vi/tin-tuc/thong-tin-suc-khoe/benh-thalassemia-co-nguy-hiem-khong/

 

 

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