title: Hemoglobin H (Hb H) disease in Canada: molecular diagnosis and review of 116 cases.
abstract: 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 (-alpha/-) or a non-deletion mutation of the alpha2-globin gene (alpha(T) alpha/-). 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.
authors.affiliation: Provincial Hemoglobinopathy DNA Diagnostic Laboratory, Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada. wayej@mcmail.mcmaster.ca
authors.forename: J S
authors.initials: JS
authors.lastname: Waye
authors.forename: B
authors.initials: B
authors.lastname: Eng
authors.forename: M
authors.initials: M
authors.lastname: Patterson
authors.forename: L
authors.initials: L
authors.lastname: Walker
authors.forename: M D
authors.initials: MD
authors.lastname: Carcao
authors.forename: N F
authors.initials: NF
authors.lastname: Olivieri
authors.forename: D H
authors.initials: DH
authors.lastname: Chui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000235:genetics*; D002170:Canada; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017085:alpha-Thalassemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D000510:Alpha-Globulins