Question

An adopted 11 year old girl of Syrian decent presented with severe illness. CBC results included a Hb 6 g/dL, MCV 55 fl and MCH 16 pg. Hemoglobin electrophoresis pattern reported HbA 2 variable and HbF 75%. The physician suspects alpha thalassemia. Given the clinical picture rank in order the 3 most likely alpha-globin genotypes and explain the molecular mechanism that leads to that genotype.

Answer 1

ALPHA THALASSEMIA:

• Blood disorder
• reduce the production of hemoglobin
• Hemoglobin is a protein which help to carry oxygen through out the body
• reduction of hemoglobin results prevention of enough oxygen rom reaching the bodys tissues
• symptoms: pale skin, weakness, fatigue etc..

Molecular nature of alpha-globin genes:

• alpha thalassemia caused by the deletion of single or double alpha globin genes or point mutation.
• 3 common types alpha globin genes :- HBA2 ,HBA1 and HBA12

alpha globin genotype and mechanism leads to that genotype:

• two alleles (/) at each alpha globin gene position is called diploid.
• MECHANISM: 2 pairs of alleles from 2 alpha globin genes 1/1(HBA1) and 2/2 (HBA2) represent the genotype (12/12) of an alpha globin gene.
• 3 genotypes: 12/12, 12/112 and 112/112
• alpha globin genotype of individual shows its -thal phenotype
• mechanism : on the basis of genotype thal can classified into 4 types

1. deletion of 4 globin genes (Hb Bart)
2. deletion of 3 globin genes (HbH disease)
3. deletion of 2 globin genes ( thal trait)
4. deletion of 1 globin genes ( thal silent)

• severity of the thal disorder indirectly connect to the number of functional globin genes