Rare Phenomenon of Psedodominance Causing Phenotypic Heterogeneity in the Expression of Delta Beta Thalassemia when Co-Inherited with Beta Mutation

Author(s):

G. Padma, K. Saroja and M. Mamata

Delta beta thalassemia is a rare form of thalassemia characterized by complex pattern of phenotypes with varying degrees of severity depending on the gene mutation involved. Hence, accurate diagnosis of the patient becomes utmost important for proper treatment and genetic counselling to the patients. Four patients (3<1 yr and 1-4 yrs) initially diagnosed as thalassemia major based on their HPLC were reinvestigated based on parents HPLC (HbF<20% in one of the parents) by molecular screening using sequencing and Gap PCR. Sequencing of all the patients for HBB gene revealed homozygosity for c.92+5G>C (IVS1-5(G>C)) mutation in three patients and c.315+1G>A in one patient. All showed heterozygosity for Asian Indian Inversion deletion ((Gγ(Aγδβ)0) when tested for delta beta deletions. One of the parents showed carrier status for beta globin mutation and the other for Gγ(Aγδβ)0 deletion. Interestingly, patients with c.92+5G>C presented early onset with low HbF as compared to the patient with c.315+1G>A, showing phenotypic diversity depending on the nature of beta mutation. Finally, patients were diagnosed as compound heterozygous for Gγ(Aγδβ)0 and beta mutation (c.92+5G>C or c.315+1G>A) representing a rare pattern of pseudo-dominance leading to wrong interpretation of the genotype of the patient and indicating the necessity of considering parents HPLC before concluding molecular diagnosis.