Wide spectrum of novel and rare hemoglobin variants in the multi‐ethnic Indian population: A review

• Published in: International journal of laboratory hematology Vol. 46; no. 3; pp. 434 - 450
• Main Authors: Thaker, Pallavi, Mahajan, Namrata, Mukherjee, Malay B., Colah, Roshan B.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2024
• Subjects: Carrying capacity; Consanguinity; Ethnicity - genetics; Genetic Variation; Hemoglobin; hemoglobin variants; Hemoglobinopathies - diagnosis; Hemoglobinopathies - genetics; Hemoglobins, Abnormal - genetics; Humans; India; Mutation; novel variants; rare variants; India; rare variants; hemoglobin variants; novel variants; India
• ISSN: 1751-5521; 1751-553X
• DOI: 10.1111/ijlh.14267

The hemoglobin (Hb) variants are qualitative abnormalities due to production of structurally abnormal globin proteins. They are categorized based on the type of mutation present in the α1, α2, β, Gγ, Aγ and δ globin genes. So far, more than 1550 Hb variants are reported in the database. They could lead to Hb polymerization, Hb instability, altered oxygen affinity and decreased oxygen‐carrying capacity of Hb or have no clinical manifestations. In India, ethnic diversity, consanguinity, regional variations and migration result in the presence of different Hb variants. We have compiled all the variants of α, β and δ globin chains in heterozygous, homozygous and in compound heterozygous forms reported from India in the last 52 years. Of the 63 rare and novel hemoglobin variants reported from India, 22 were α‐globin chain variants, 37 were β‐globin chain variants and 4 were δ‐globin chain variants. Twelve novel Hb variants (Hb J Rajappan, Hb Koya Dora, Hb Rampa, Hb Godavari, Hb Chandigarh, Hb D Agri, Hb Lucknow, Hb Vellore, Hb Midnapore, Hb Bijnor, Hb A2Tianhe and Hb A2Saurashtra) were identified among persons of Indian origin. Majority of them were picked up on HPLC. Some of the variants like Hb Titusville, Hb Shimonoseki, Hb Chandigarh, Hb D Agri, Hb Yaizu and Hb Vellore eluted in the HbS window whereas variants like HbD Iran, Hb St. Louis, Hb G Coushata, HbM Saskatoon, Hb Lucknow, Hb Grange‐Blanche and Hb Tianshui showed falsely elevated HbA2. Hence, careful and systematic investigations are required to identify them.