In our cohort of NAFLD patients we detected several individuals that were resistant to polymerase chain reaction (PCR) amplification of PNPLA3. PCR failure in those patients was specific to the PNPLA3 region alone, and could not be explained by degraded or poor quality DNA; suggesting that a novel DNA alteration may be involved. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.