ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype

Haploinsufficiency phenotype comments:

Autosomal recessive type defects (including homozygous or compound heterozygous intragenic CNCs and whole gene deletions) of HBA2 cause Alpha-thalassemia. Deletion of both ?-globin genes (i.e. HBA1 and HBA2) on chromosome 16: More than 20 different deletions ranging from approximately 6 kb to more than 300 kb and removing both ?-globin genes (and sometimes embryonic HBZ) have been reported. In the homozygous state these deletions result in Hb Bart syndrome. When any of these alleles occur in combination with another allele carrying a single ?-globin gene deletion the result is HbH disease (GeneReviews). Hemoglobin Bart hydrops fetalis (Hb Bart) syndrome, the most severe form of ?-thalassemia, is characterized by fetal onset of generalized edema, ascites, pleural and pericardial effusions, and severe hypochromic anemia, in the absence of ABO or Rh blood group incompatibility. It is usually detected by ultrasonography at 22 to 28 weeks' gestation and can be suspected in an at-risk pregnancy at 13 to 14 weeks' gestation when increased nuchal thickness, possible placental thickness, and increased cardiothoracic ratio are present. Death in the neonatal period is almost inevitable. All four ?-globin alleles are deleted or dysfunctional (inactivated). Of note, in certain instances, carriers may display an ?-thalassemia trait hematologic phenotype. Please see GeneReviews for more detailed information.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No literature identified.