Discussion Forums > Thalassemia Major
Again!
sydneygirl:
Hi Christine,
Thats great to hear lauryns hb went up! take care of lauryn all the best!
:wink
Andy Battaglia:
Hi Christine,
It is true that Hb can drop with infections so that may explain that original drop. Some bacterial infections can actually cause hemolysis, the breaking down of red blood cells, although normally symptoms would be noted. Factors such as temporary dehydration, which is not uncommon in infants, can also play a role in lowered Hb. Whatever the cause in Lauryn's case, it did seem to be short term.
From what you've been told it sounds like the two genes work as modifiers of what each other does, leading to thalassemia major. I would like to know more about Lauryn's DNA testing. Were you told which chromosomes these genes occur on? Before you asked for my input I had already spent hours trying to find mention of these genes, and at best I found mention that they exist, which is often the case with the specific thal mutations. Their existence is cataloged but not much information about effects is available. However, DNA testing is how the effects of these deletions will also be eventually cataloged. If you have any other information from the DNA tests, such as anything that contains the term, IVS, let me know. For example, IVS2-745C>G.
Narendra:
--- Quote ---we got the DNA results: she is definitley Thal major.
its VERY complicated to explain but according to the md, lauryns mutation is very unusual.
one of us (husband or I) carry the nt168 gene
and the other nt365+45
the results say:
IF NT168C-T AND NT365=745C-G ARE ON OPPOSITE CHROMOSONES, THE MOLECULAR RESULTS WOULD BE CONSISTENT WITH BETA THALASSEMIA. TAREGETED TESTING OF THE PATIENTS PARENTS WOULD CONFIRM THE ORIENTATION OF THESE SEQUENCE VARIATIONS.
NO EVIDENCE OF THE 619BP DELETION OF THE B-GLOBIN GENE IDENTIFIED
--- End quote ---
Christine,
Lauryn amazes me with her stable hemoglobin, which is a good sign. The lesser the transfusion requirement the better it is.
Do you know what type of DNA test was done? Was it for Alpha Thal or Beta Thal?
Christine Mary:
beta thal, i believe narendra
johns hopkins hospital did the dna test.
the other part of the results say:
FULL SEQUENCING OF THE CODING REGIONS OF THE HBB (BETA GLOBIN) GENE AND ANALYSIS FOR 619BP DELETION INDENTIFICATION OF MUTATIONS ASSOCIATED WITH B-THALASSEMIA AND B-GLOBIN STRUCTURAL VARIANTS.
POSITION NORMAL PATIENT
NT20 C C/T
NT168 C C/T
NT365=745 C C/G
INTERPRETATION:
NT20C-T :NOT A REPORTED MUTATION OR POLYMORPHISM, BUT WE HAVE SEEN THIS VARIATION IN SEVERAL FAMILIES ON THE SAME CHROMOSONE AS NT365=745C-G.THE CLINICAL SIGNIFICANCE OF THIS VARIATION IS UNCERTAIN.
NT168C-T(Q39X):PREVIOUSLY REPORTED NONSENSE MUTATION
NT365=745-G(INTRON 2):PREVIOUSLY REPORTED SPLICING MUTATION
there is a reference on the paper as well:
http://globin.cse.psu.edu/html/huisman/thals/beta/codon.39.(c-@t).cag(gln)@TAG
NT20
Andy Battaglia:
Christine,
Both of these mutations cause aberrant messenger RNA to be produced, resulting in defective beta globin protein chains that damage the red blood cells. Of great interest is that there has been much research into correcting this, as this mutated mRNA is at the root of many genetic diseases.
From http://www.pnas.org/cgi/content/abstract/97/17/9591
--- Quote ---Mononuclear cells from peripheral blood of thalassemic patients were treated with morpholino oligonucleotides antisense to aberrant splice sites in mutant beta -globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of beta -globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients with IVS2-654/beta E, IVS2-745/IVS2-745, and IVS2-745/IVS2-1 genotypes. The maximal Hb A level for repaired IVS2-745 mutation was approx 30% of normal; Hb A was still detectable 9 days after a single treatment with oligonucleotide. Thus, expression of defective beta -globin genes was repaired and significant level of Hb A was restored in a cell population that would be targeted in clinical applications of this approach.
--- End quote ---
These thal mutations are mainly Mediterranean in origin and are quite different from many other thal mutations. While this research holds promise for restoring normal hemoglobin in people with these types of mutations, it would not be useful for thal mutations where beta hemoglobin isn't produced. I have heard before that thalassemia is actually many different disorders under one label and this is a perfect example of what this means. In thalassemia caused by these mutations, it is actually an mRNA defect in the hemoglobin rather than an inability to produce beta hemoglobin.
Interestingly, with this type of thal, the presence of alpha thal trait can actually be a moderating factor, leading to a less severe thalassemia.
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