The genetic basis of asymptomatic codon 8 frame-shift (HBB:c25_26delAA) β(0) -thalassaemia homozygotes

British Journal of Haematology
Zhihua JiangD H K Chui

Abstract

Two 21-year old dizygotic twin men of Iraqi descent were homozygous for HBB codon 8, deletion of two nucleotides (-AA) frame-shift β(0) -thalassaemia mutation (FSC8; HBB:c25_26delAA). Both were clinically well, had splenomegaly, and were never transfused. They had mild microcytic anaemia (Hb 120-130 g/l) and 98% of their haemoglobin was fetal haemoglobin (HbF). Both were carriers of Hph α-thalassaemia mutation. On the three major HbF quantitative trait loci (QTL), the twins were homozygous for G>A HBG2 Xmn1 site at single nucleotide polymorphism (SNP) rs7482144, homozygous for 3-bp deletion HBS1L-MYB intergenic polymorphism (HMIP) at rs66650371, and heterozygous for the A>C BCL11A intron 2 polymorphism at rs766432. These findings were compared with those found in 22 other FSC8 homozygote patients: four presented with thalassaemia intermedia phenotype, and 18 were transfusion dependent. The inheritance of homozygosity for HMIP 3-bp deletion at rs66650371 and heterozygosity for Hph α-thalassaemia mutation was found in the twins and not found in any of the other 22 patients. Further studies are needed to uncover likely additional genetic variants that could contribute to the exceptionally high HbF levels and mild phenotype in thes...Continue Reading

References

Dec 1, 1992·Human Genetics·M A CürükT H Huisman
Jan 1, 1989·Acta Haematologica·A GurgeyT H Huisman
Mar 1, 1994·Journal of Medical Genetics·A M KulievB Modell
Feb 15, 2002·British Journal of Haematology·D J Weatherall
Jun 27, 2003·American Journal of Hematology·Wafaa LemsaddekLeonor Osório-Almeida
Mar 11, 2004·Hemoglobin·Wafaâ LemsaddekLeonor Osório-Almeida
Apr 7, 2009·British Journal of Haematology·Swee Lay Thein, Stephan Menzel
Oct 29, 2009·Nature Genetics·Santhi K GaneshJing-Ping Lin
Apr 15, 2011·Blood·Idowu AkinsheyeMartin H Steinberg
Jan 1, 2010·Molecular Biology International·Nasir A S Al-AllawiJaladet Jubrael
Dec 12, 2012·Journal of Community Genetics·Hanan A Hamamy, Nasir A S Al-Allawi
Mar 13, 2014·The Journal of Clinical Investigation·Ralph StadhoudersEric Soler

❮ Previous
Next ❯

Citations

Jan 9, 2018·Journal of Pediatric Hematology/oncology·Anthony O AkinbamiMartin H Steinberg
Feb 28, 2017·British Journal of Haematology·Zhihua JiangDavid H K Chui

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.