As described in the question stem, this mutation occurs within an intron (a gene segment which is transcribed [DNA->RNA] but not translated). RNA splicing enzyme(s) grab RNA and “loop it”; an intron is cut out and the exons on either side of the intron are adjoined, like this:

exon1—intron—exon2 => exon1—exon2

Typically, this splicing occurs at the very edges of the intron (what I denoted with the “—” character). But in our case, a mutation within the intron is causing RNA splicing enzyme to recognize a new site: the splicer cuts within the intron (instead of at the very edge, as it should). So, we get something that looks like this:

exon1—intr—exon2

That’s a totally different mRNA molecule, and it's going to make our β-globin protein look (and behave) awfully strange.

This has to do with intron splicing. Remember GTAG. This mutation induced an AG closer where it was supposed to be, so some of that intron just became an exon.

I interpreted "sequence surrounding first two exons of gene" - to mean they must be talking about introns. Three of the answer choices don't have much to do with introns.

• missense mutation would have to be in the exon to cause change in amino acid.
• polyadenylation is at the end of the mRNA
• inhibition of replication is DNA

that may not be air tight, but helps narrow down. Also knowing some B-thalassemia is due to variants in abnormal splicing helps. (FA 2019 pg 43)

also remember that B-thalassemia is due to point mutations in splice sites and promoter sequences (FA19 pg410). If you create a mutation in a splice site you will surely mess up the correct mRNA needed to make a functional B-globin protein. That is how I answered the question.