Hemoglobin H (Hb H) disease in Canada: Molecular diagnosis and review of 116 cases

Over the past decade, we have characterized at the DNA level a total of 116 hemoglobin H (Hb H) disease patients living in Canada. The majority of patients were of southeast Asian descent (Chinese, Filipino, Laotian, Vietnamese), with a small number being of Mediterranean, Middle Eastern or East Indian background. A total of 15 distinct genotypes were detected, all but one being compound heterozygotes for a two‐gene cis deletion and a single‐gene deletion (‐α/−) or a non‐deletion mutation of the α2‐globin gene (α T α/−). Seven different two‐gene cis deletions were encountered, along with nine single‐gene deletions and point mutations. The wide range of mutations associated with Hb H disease in Canada is a reflection of the population heterogeneity. The diagnosis of Hb H disease at the molecular level is important with respect to genetic counseling and the identification of families at risk for having pregnancies affected with Hb Bart's hydrops fetalis syndrome and/or Hb H disease. Six of the Hb H disease patients in our cohort had spouses who carried single‐gene deletions, making these couples at risk for having children with Hb H disease. More important, seven patients had partners who carried two‐gene cis deletions. These couples are at reproductive risk for both Hb Bart's hydrops fetalis syndrome and Hb H disease. Am. J. Hematol. 68:11–15, 2001. © 2001 Wiley‐Liss, Inc.