Background and Aims:
A 3month old female child, borne of non-consanguineous marriage, presented with clinical features suggestive of beta-thalassemia major and was re-confirmed on investigation at 6months. Full beta gene sequencing showed IVS1-1(G>C) (Hb Monroe) and c.-92(C>G). The mother was beta thalassemia trait while the father showed mildly elevated HbF levels.

Methods:
Complete-haemogram of the patient and parent’s was done along with hemoglobin electrophoresis using HPLC system. Genomic DNA was isolated from blood leukocytes and Multiplex-ARMS-PCR for common 5 mutations: 619bp deletion, IVS1-5(G>C), IVS1-1(G>T), FS 8/9(+G), FS 41/42(-CTTT) was performed. The Beta-globin gene was amplified via PCR and bi-directional sequencing of the exons along IVS 1&2 was performed and analyzed. HbVar database was used for the identification of mutations. HBG-XMn1 and -68(C>T) variants were identified. Detection of deletions causing delta-beta-thalassemia and HPFH was determined. Uniparental-disomy was excluded.

Results:
The patient was homozygous for IVS1-1(C>G) (Hb Monroe) and its associated mutation c.-92(C>G) despite the mother being heterozygous for the same mutations while the father showed the HBG-Xmn1 polymorphism (rs7482144A>G), representative of the Arab-Indian haplotype which is associated with higher HbF levels was seen in heterozygous state. There was a strong possibility of deltabeta deletional mutation in the father. This could most plausibly explain the presence of homozygosity in patient for IVS1-1(G>C).

Homozygous Hb Monroe - A rare mutation in a Thalassemic child of Goan origin: A case report and family study