Compound Heterozygosity for a Mild β⁺ and a Rare β°-Thalassemia Allele

Abstract

Hematological and hemoglobin composition data are presented for 14 members of a Surinam family (and for 1 unrelated subject) with either a β-thalassemia heterozygosity [5 with the -29 (A – G) β⁺ mutation and 5 with the IVS II-849 (A→G) β° mutation] or a compound heterozygosity (the 5 remaining patients). Identification of the mutation was by hybridization of amplified DNA with ³²P-labelled synthetic oligonucleotides. The data indicate distinct differences between the two groups of heterozygotes, mainly in degree of microcytosis and hypochromia, in Hb A₂ level, and in the level of ^Gγ (high in the -29 heterozygotes and low in the IVS II-849 heterozygotes). The 5 compound heterozygotes had a thalassemia intermedia with high Hb F levels (high ^Gγ), elevated Hb A₂, and Hb A levels comparable to those seen in patients with a homozygosity for the -29 mutation or with the combination of this β⁺-thalassemia and Hb S. An α-thalassemia-2 heterozygosity (-3.7 kb deletion) was present in 2 patients. Their hematological data were improved over those for the patients with four α globin genes; one was the mother of two sets of twins. The high ^Gγ value in the Hb F of the compound heterozygotes suggests that the high Hb F production in the condition is mainly directed by the chromosome with the – 29 (A – G) mutation.

COMBINATION OF IVS2.849 A-G WITH IVS1.1 G-A: A Mutation of β-Globin Gene in a Turkish β-Thalessemia Major Patient

“…This mutation is reported in American Black families and families from Surinam, Guadeloupe [4][5][6][7]. Here, we report clinical findings of compound heterozygosity of this splice site mutation (i.e., IVS2.849 A-G) and another splice site mutation IVS1.1 A-G.…”

“…Athweh et al performed functional analysis of this mutant gene obtained from a Black patient, and showed that the mutation inactivated normal acceptor splice site and resulted in some utilization of a cryptic splice site near position 580 of IVS2 [5]. This mutation was later described in a Surinam Creole family [6]. Lastly, Romana et al have found this mutation in 2 families from Guadeloupe, which is an island in the Caribbean with a population admixture of West African, Asian Indian, and Caucasian ancestry [7].…”

Origin of the codon 47 (+A) β‐thalassaemia mutation among the Nicobarese of the Andaman and Nicobar islands in India

“…Hence, unusual genetic combinations involving certain genetic defects that are generally prevalent in South‐East Asia are seen in this population. The presence of −SEA deletion causing Hb H disease (Giordano et al , 1997) and the presence of the −29 (A→G) β ‐thalassaemia mutation (Codrington et al , 1990), which are present in the Chinese population, are some examples. It is conjectured that the codon 47 (+A) mutation must have migrated to Suriname about 200–300 years ago during the slave trade.…”