LAUSR

Adult hemoglobin (HbA) is a tetramer formed by the association of a and b chains (a2b2) which are encoded onto different loci. The two a adult genes, HBA1 and HBA2, are located on chromosome 16 and the adult b gene (HBB) on chromosome 11. The a genes encode for an identical amino acid sequence and arise from a common ancestor, displaying a very high homology at the nucleotide level. The nucleotide homology gives the possibility for adequate and inadequate pairing and genetic recombination, leading to equal or unequal exchanges of material or to a gene conversion, one allele being used to modify the other one [1]. Both loci are regulated so that the globins produced from the a-genes and the b-genes associate together to produce the Hb tetramer, and precise quantification of a variant Hb can give some additional information on the mutated gene. An a-chain mutant is expected to be expressed at 20–25%, depending upon the affected gene, and a b-chain mutant at 40–50%. Usually, Hb variants are detected using their changes in physicochemical properties resulting from the amino acid modification(s) compared to the wild type. Among the various methods available, two automated ones are now almost exclusively used in the routine analysis of Hb variants: cation-exchange HPLC (CE-HPLC) and capillary electrophoresis (CE). These methods can lead to a putative identification of a variant, but this approach should be considered with caution as an identical modification of mobility can be produced by several amino acid changes. However, in many cases, it is not possible to correctly identify a variant just by using the data obtained from CE-HPLC and CE. This fact is of importance when pathologic variants are involved and particularly Hb S (b6 Glu>Val HBB:c.20A>T) because variants which mimic Hb S are regularly reported [2, 3]. From the consequences of chromosome pairing, the gene conversion, which involves a nonreciprocal transfer of information from a donor sequence to an acceptor sequence, is a rarely described event between the two homologous a-globin genes. A few examples have been published concerning the patchwork alleles a121, a212, and a12 variants [4] in which a1 is the portion encoded by HBA1 and a2 that encoded by HBA2. If the a-gene involved carries a mutation, the gene conversion can produce an atypical configuration where two copies of the same variant are transmitted together resulting in a higher expression level of the a-variant [4, 5]. Delimitation of the converted sequence can be found by searching the mutation and SNPs specific of HBA1 or HBA2. We report here a new a-gene conversion duplicating the Hb Arya mutation (c.142G>A) labeled by a star (*): (a2 a1/a1*2a1*) in a child and his father originated from Azerbaijan. Hb Arya is a rare variant previously described in a family from Iran without precision on the affected gene. Its electrophoretic mobility is very close to that of Hb S, and, in the original publication, it amounted to 22% [6]. Due to the gene conversion, the proband electrophoretic pattern perfectly mimicked that of an Hb S carrier.