While it is likely that only a small number of mutations are driver mutations and the rest are passengers, our model accounts for the contribution of every potential mutation in a normal distribution and, from this, the collective roles played by all mutations can be quantified.
In summary, the F5 G1718S mutation causes a normal APC ratio despite the presence of a heterozygous F5 R506Q mutation – described as a "pseudo-wild-type" FVL.
Furthermore, the H66A mutation showed a normal kpep value when assayed with Ala-tRNAAla, indicating that the mutation does not hinder the ribosome from performing peptide bond formation in some unknown manner.
This novel technique, called CRISPR, introduces experimentally controlled and transient damage to the mutated DNA of patient cells and exploits naturally occurring DNA repair mechanisms to transform the disease-causing mutation to a normal state.
(Supporting Information Data S1) In the index subject, a heterozygous F5 R506Q mutation but a normal APC ratio were detected (Fig 1).
In contrast, the individual with a PPP2R5B mutation had a normal head circumference but was very tall with a height three standard deviations above the mean (Table 1).
Indeed studies performed on fibroblasts from patients carrying the homozygous W437X (Trp → Xxx) nonsense PINK1 mutation revealed a normal mitochondrial tubular network (Piccoli et al, 2008).
Another adult subject had an APOB mutation with a normal lipid profile: serum cholesterol 161 mg/dL (normal <200), LDL 93 mg/dL (normal <100) and HDL 56 mg/dL (high risk <40, low risk ≥60).
It is believed that Huntington's disease is caused by a mutation from a normal huntingtin gene to a mHtt gene expressing aggregation-prone mHtt proteins with polyglutamine (polyQ) expansion.
In this circumstance, a breast tumor showing loss of expression of an MMR gene by IHC would indicate a significant likelihood of an underlying germline mutation, while a normal MMR gene result would not rule out Lynch syndrome.
