Beginner questions on RNA-seq DEG

[[email protected]]

Currently, I have the following RNA samples and want to see any up/down-regulated gene expression in proband to explain the disease-causing of the proband.

Sample1: (Proband) blood
Sample2: (Proband) fibroblast
Sample3: (Control person #1) blood
Sample4: (Control person #1) fibroblast
Sample5: (Control person #2) blood
Sample6: (Control person #2) fibroblast
Sample7: (Control person #3) blood
Sample8: (Control person #3) fibroblast

In this case,
1. Can I do the DEG? Any tool suggested in this case (cuff/DESeq/edgeR)
2. Can I treat control samples as biological replica of proband?
3. Is it statistically significant? And any way to improve?

Thanks a lot!