Thalassemia in Western Australia: 11 novel deletions characterized by Multiplex Ligation-dependent Probe Amplification

Novel large deletions in the human α-globin gene cluster: Clarifying the HS-40 long-range regulatory role in the native chromosome environment

“…2B) whose sequence is not found in the human genome (http://www.ncbi.nlm.nih.gov/blast/ BLAST.cgi). Interestingly, very recently, an Australian immigrant case was described, presenting this same deletion/insertion rearrangement pattern in one allele [15]. Although the 39nt sequence was not reported, and given the rarity of this kind of events, we presume that it was the same rearrangement described here.…”

“…The spectrum of clinical severity of this condition depends on the number of α-genes being deleted, either one or two per allele, resulting in α + -thal or α 0 -thal, respectively. However, not very often, α 0 -thal may also occur due to deletion of the upstream regulatory elements resulting in a severe downregulation of the α-globin gene expression [11][12][13][14][15].…”

Homozygous deletion of the major alpha-globin regulatory element (MCS-R2) responsible for a severe case of hemoglobin H disease

“…[2][3][4][5][6][7] It has been shown experimentally that deletion of MCS-R2 alone is sufficient to down-regulate alpha-globin expression to less than 3% of normal, consistent with the notion that MCS-R2 is the most important regulatory element. 8,9 In our patient, the homozygous deletion of MCS-R2 is associated with HbH disease, a phenotype less severe than expected from the predicted reduction of alpha-globin chain expression.…”

The Molecular Basis of -Thalassemia

“…Recently, an even smaller deletion, which removes 3.3 kb of DNA including MCS-R2 but no other MCS-R element, was described (see Fig. 1) (Phylipsen et al 2010). The phenotype (HbH disease) of the proband, which carries the same small deletion on both copies of chromosome 16, is consistent with expression of both cis-linked a genes being down-regulated but not completely abolished (Coelho et al 2010).…”