I occasionally run into mention of the triplicate alpha genes and they definitely have an effect on beta thals, although sometimes the effect is positive and sometimes negative. It seems to be dependent on which beta thal gene(s) co-exist with the triplicate alpha gene. And reviews of different patients has sometimes led to conflicting results about what effect the alpha gene has. One study that examined these combinations can be found at http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=22792&Ausgabe=225922&ProduktNr=224250
coexistence of heterozygosity for alpha-gene triplication and beta-thalassemia intermedia
In the literature there have been several reports about the patients with a beta-thalassemia intermedia-like clinical picture associated with homozygous alpha-gene triplication interacting with a severe beta-thalassemia mutation [6, 12]. However, there are conflicting results regarding the phenotypic expression of combinations of a severe heterozygous beta+- or beta0-thalassemia mutation with one additional alpha-gene [4, 6, 8, 11, 12, 13, 14].
In our patients with beta-TI associated with beta-39 and beta-101 mutations (patients 6 and the sibling of family 5) HbF value was higher in the one with the triplicated alpha-gene (patient 6). However, it seems that elevation of the HbF value did not ameliorate expression of the disease. On the contrary the disease was even more severe in the patient with triplication of the alpha-gene as far as Hb value, jaundice and splenic enlargement were concerned (table 2). This observation suggests that a triplicated alpha-gene interacts with a mild beta-thalassemia compound heterozygote to cause a more severe disease than is seen in patients with a normal alpha-gene number (tables 1, 2).
coexistence of alpha-gene triplication and beta-thalassemia trait
In patient 7 (the father of family 5), the triplication of the alpha-gene did not seem to modify any parameters that characterize the heterozygous expression of the beta-39 thalassemia mutation. Contrary to our observation, a similar genetic composition was reported to be associated with severe trait conditions by Beris et al. .
In patients 8, 10 and 11 the hematological expression of the heterozygous state of IVSI-1 was greatly modified by triplicated alpha genes. In these subjects the beta-thalassemia trait was associated with a thalassemia intermedia-like phenotypical expression which was characterized by lower Hb and increased HbF values as compared with those of the simple beta-thalassemia trait of IVSI-1 mutation (table 2) . Moreover, hematological expression in our patients was as severe as for those patients with heterozygosity for IVSI-1 and coexistent homozygosity for alpha-gene triplication reported previously [6, 12]. Our study indicated that in 3 of 4 heterozygotes associated with severe beta-thalassemia mutation coexistence of alpha-gene triplication resulted in thalassemia intermedia-like condition. The effect of alpha-gene number on the expression of the two deltabeta-thalassemia traits (family 4), one with alpha-thalassemia and the other with a triplicated alpha-gene was again evident from the variations in HbF values (table 2). However, it was interesting that the MCV value (table 2) was higher in the subject with triplicated alpha-gene than the one with alpha-thalassemia.
Jean, do you know which beta gene mutation you have?
While alpha thal is more common among Asians, it is also found among Mediterranean people. I ran into this study on a Greek population.http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3755006&dopt=AbstractPlus
Frequency of alpha-thalassemia in Greece.
Kanavakis E, Tzotzos S, Liapaki A, Metaxotou-Mavromati A, Kattamis C.
Using hematological and gene mapping techniques, a cord blood survey was carried out to estimate the frequency of alpha-thalassemia in the Greek population. Out of 227 newborns studied, 16 (7.05%) were found by gene mapping to be alpha-thalassemia 2 heterozygotes (-alpha/alpha alpha), and of these only two had increased levels of hemoglobin Bart's in the cord blood (1.2 and 2.0%). Similarly, one heterozygotes for the common Mediterranean alpha-thalassemia 1 haplotype (-/alpha alpha) and one for the 20.5-kb deletion type (-(alpha)20.5/alpha alpha) were found, showing increased levels of Bart's of 4.8 and 6.6%, respectively. Four (1.76%) heterozygotes for the triple alpha gene arrangement (alpha alpha alpha/alpha alpha) were found. One individual with a level of Bart's in the cord blood of 8% was found to be a double heterozygote for alpha-thalassemia 2 and a dysfunctional alpha gene arrangement (-alpha/-(alpha)?). These results give an overall incidence for alpha-thalassemia in the Greek population of 8.4%.
PMID: 3755006 [PubMed - indexed for MEDLINE]
A combination of genes such as this, illustrates so well why this information needs to be known and also passed onto all descendants. Combinations of beta and alpha thalassemia gene mutations can be passed onto children and the carriers should be very aware of the possibilities.