IthaID: 1217

Context nucleotide sequence:
TGTGCTGGCCCATCACTTTGGCAAA [G>C] AATTCACCCCACCAGTGCAGGCTGC (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKQFTPPVQAAYQKVVAGVANALAHKYH

Also known as: Hb D-Chicago, Hb D-North Carolina, Hb D-Portugal, Hb D-Los Angeles, Hb Oak Ridge

Comments: Association of Hb D-Punjab with another abnormal haemoglobin or β-thalassaemia allele leads to clinical symptoms ranging from mild to moderate disease, resembling either thalassemia minor or thalassemia intermedia. Association with the sickle mutation leads to a severe form of SS disease since Hb D-Punjab (β121Glu>Gln) enhances the polymerization of Hb S (with an effect trans to the Val-β6 in the contact site). No clinical or haematological alterations in heterozygosity or homozygosity. Double heterozygous HbS/Hb D-Punjab individuals from Badagas (an indigenous community of Nilgiris - India) also presented with heterozygous beta-globin BP1U distal promoter motif (AT)x (T)y (-530 cap site). The HbS gene associated with the Arab-Indian haplotype. The linkage of HbS with the (AT)9 (T)5 BP1U Arab-Indian haplotype reduces sickle gene expression and induces HbF, resulting in lesser sickle disease intensity. These genetics are also suggestive of a Harappan origin for the Badagas [PMID: 35221311].

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Heterozygous records (preview in IthaPhen)

1. LEHMANN H, Three varieties of human haemoglobin D., Nature , 182(4639), 852-4, 1958 PubMed
2. BOWMAN B, INGRAM VM, Abnormal human haemoglobins. VII. The comparison of normal human haemoglobin and haemoglobin D-Chicago., Biochim. Biophys. Acta , 53(0), 569-73, 1961 PubMed
3. STOUT C, HOLLAND CK, BIRD RM, HEMOGLOBIN D IN AN OKLAHOMA FAMILY., Arch. Intern. Med. , 114(0), 296-300, 1964 PubMed
4. Schneider RG, Ueda S, Alperin JB, Levin WC, Jones RT, Brimhall B, Hemoglobin D Los Angeles in two Caucasian families: hemoglobin SD disease and hemoglobin D thalassemia., Blood , 32(2), 250-9, 1968 PubMed
5. Lehmann H, Carrell RW, Variations in the structure of human haemoglobin. With particular reference to the unstable haemoglobins., Br. Med. Bull. , 25(1), 14-23, 1969 PubMed
6. Ozsoylu S, Homozygous hemoglobin D Punjab., Acta Haematol. , 43(6), 353-9, 1970 PubMed
7. Imamura T, Riggs A, Identification of hemoglobin Oak ridge with hemoglobin D Punjab (Los Angeles)., Biochem. Genet. , 7(2), 127-30, 1972 PubMed
8. Bunn HF, Altman AJ, Stangland K, Firshein SI, Forget B, Schmidt GJ, Jones RT, Hemoglobins Aida (alpha 64 Asp leads to Asn) and D-Los Angeles (beta 121 Glu leads to Gln) in an Asian-Indian family., Hemoglobin , 2(6), 531-40, 1978 PubMed
9. Worthington S, Lehmann H, The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members., J. Med. Genet. , 22(5), 377-81, 1985 PubMed
10. Husquinet H, Parent MT, Schoos-Barbette S, Dodinval-Versie J, Lambotte C, Galacteros F, Hemoglobin D-Los Angeles [beta 121(GH4)Glu----Gln] in the Province of Liège, Belgium., Hemoglobin , 10(6), 587-92, 1986 PubMed
11. Li HJ, Liu DX, Li L, Liu ZG, Lo SL, Zhao J, Han XP, Yu WZ, A note about the incidence and origin of Hb D-Punjab in Xinjiang, People's Republic of China., Hemoglobin , 10(6), 667-71, 1986 PubMed
12. Harano T, Harano K, Ueda S, Nakaya K, Hb D Los Angeles [beta 121 Glu----Gln] in Japan., Hemoglobin , 11(2), 177-80, 1987 PubMed
13. Zeng YT, Huang SZ, Ren ZR, Li HJ, Identification of Hb D-Punjab gene: application of DNA amplification in the study of abnormal hemoglobins., Am. J. Hum. Genet. , 44(6), 886-9, 1989 PubMed
14. Schnee J, Aulehla-Scholz C, Eigel A, Horst J, Hb D Los Angeles (D-Punjab) and Hb Presbyterian: analysis of the defect at the DNA level., Hum. Genet. , 84(4), 365-7, 1990 PubMed
15. Fucharoen S, Changtrakun Y, Surapot S, Fucharoen G, Sanchaisuriya K, Molecular characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand., Hemoglobin, 26(3), 261-9, 2002 PubMed
16. Gupta A, Saraf A, Dass J, Mehta M, Radhakrishnan N, Saxena R, Bhargava M, Compound heterozygous hemoglobin d-punjab/hemoglobin d-iran: a novel hemoglobinopathy., Indian J Hematol Blood Transfus , 30(0), 409-12, 2014 PubMed
17. Archana R, Vidya C, Sumithra N, Jyothi M, Sanil R, Arab-Indian -530 ß-distal promoter haplotype and sickle/Hb D heterozygosis in Badagas of Nilgiris: is it suggestive of Harappan origin?, J Genet, 101(0), 0, 2022 PubMed