Hb Jeddah [α68(E17)Asn→His (α1)]: A Newly Recognized α Chain Variant, Seen in Combination with Hb S [β6(A3)Glu→Val], and Found in Three Separate Families of Middle Eastern Origin

Abstract

We report a previously unrecognized alpha chain variant identified in three families from Saudi Arabia, Yemen and Abu Dhabi. The index patient presented for hemoglobinopathy screening and was identified to have both this novel alpha chain variant and Hb S [beta6(A3)Glu-->Val, GAG(-->)GTG]. Hb Jeddah results from a point mutation (AAC(-->)CAC) at codon 68 in exon 2 of the alpha1 gene. There were no apparent hematological abnormalities or clinical symptoms in the three individuals identified as heterozygotes for Hb Jeddah, as well as the index case with both Hb S and Hb Jeddah. As we have found this variant in three separate families, the incidence may be greater than currently recognized.

Mutations in the paralogous human α-globin genes yielding identical hemoglobin variants

“… [ 31 ] Hb Jeddah Yemenite 1 11.6 90.3 19.6 – – – [ 31 ] Hb Jeddah Emirati (Abu Dhabi) 1 12.6 72.9 N.A. – – – [ 31 ] p.D75Y (c.226G>T) Hb Winnipeg American 10 12.9 ± 1.3 90.7 ± 6.8 14.1 ± 0.6 – – – 1.3 [ 32 ] Hb Winnipeg French 38 13.0 ± 1.9 91.2 ± 7.3 13.0 ± 0.7 – – – This report Hb Winnipeg French 11 13.6 ± 0.8 91.9 ± 6.7 – 16.9 ± 0.9 – – This report Hb Winnipeg Greek 1 13.6 88.9 – 16.1 – – This report p.P77H (c.233C>A) Hb Toulon African 1 9.8 94.4 23 – – – 1.08 This report Hb Toulon British 1 13.3 91 – 26.3 – – This report ...…”