Homozygous hemoglobin Monroe (codon 30 G>C) in a child of Goan (Indian) origin: A case report and family study

India has a huge burden of β-thalassemia with an estimated 100,000 patients and a prevalence of 3%–4% carriers. The five common mutations reported in the India are IVS 1–5 (G->C), IVS 1-1 (G->T), codon 41/42 (-TCTT), codon 8/9, and 619 bp deletion. We report this rare case of IVS 1-1 G>C variant (hemoglobin [Hb] Monroe) in homozygous form in a child of Goan origin. The propositus presented at 3 months with pallor, hepatosplenomegaly, and lymphadenopathy. Diagnostic workup of the child was suggestive of β-thalassemia major, the parents Hb electrophoresis revealed β-thalassemia trait in the mother, whereas the father had elevated HbF levels. Initial polymerase chain reaction by ARMS (amplification-refractory mutation specific) was negative for the common five mutations. β-globin full gene sequencing revealed the presence of IVS-1-1G>C (Hb Monroe) in the homozygous form and also c.-92 C>G in the homozygous form, the mother was heterozygous for both the mutations, whereas the father was negative. STR marker studies did not indicate uniparental disomy to be the reason for IVS-1-1 G>T homozygosity in the child in the absence of the same mutation in the father. The father showed a possibility of δβ deletional mutation. This report highlights the importance of molecular studies in participants with borderline HbA2 levels, including spouse of a typical β-thalassemia carrier. Assaying for only the common five mutations may not yield complete answers. Full gene sequencing should be performed in those individuals with a strong phenotype of β-thalassemia. The prenatal diagnosis should be offered to couples at risk