Although cells undergo multiple steps in order to ensure there are no mutations in the genetic sequence, sometimes specific deletions and other genetic changes during Okazaki fragment maturation go unnoticed. Because Okazaki fragments are the set of nucleotides for the lagging strand, any alteration including deletions, insertions, or duplications from the original strand can cause a mutation if it is not detected and fixed. Other causes of mutations include problems with the proteins that aid in DNA replication.  For example, a mutation related to primase affects RNA primer removal and can make the DNA strand more fragile and susceptible to breaks. Another mutation concerns polymerase α, which impairs the editing of the Okazaki fragment sequence and incorporation of the protein into the genetic material. Both alterations can lead to chromosomal aberrations, unintentional genetic rearrangement, and a variety of cancers later in life.
In order to test the effects of the protein mutations on living organisms, researchers genetically altered lab mice to be homozygous for another mutation in protein related to DNA replication, flap endonuclease 1, or FEN1. The results varied based on the specific gene alterations. The homozygous knockout mutant mice experienced a "failure of cell proliferation" and "early embryonic lethality" (27). The mice with the mutation F343A and F344A (also known as FFAA) died directly after birth due to complications in birth including  pancytopenia and pulmonary hypoplasia. This is because the FFAA mutation prevents the FEN1 from interacting with PCNA (proliferating cell nuclear antigen), consequently not allowing it to complete its purpose during Okazaki fragment maturation. The interaction with this protein is considered to be the key molecular function in the FEN1's biological function. The FFAA mutation causes defects in RNA primer removal and long-base pair repair, of which cause many breaks in the DNA. Under careful observation, cells homozygous for FFAA FEN1 mutations seem to display only partial defects in maturation, meaning mice heterozygous for the mutation would be able to survive into adulthood, despite sustaining multiple small nicks in their genomes. Inevitably however, these nicks prevent future DNA replication because the break causes the replication fork to collapse and causes double strand breaks in the actual DNA sequence. In time, these nicks also cause full chromosome breaks, which could lead to severe mutations and cancers. Other mutations have been implemented with altered versions of Polymerase α, leading to similar results.