Defects in DNA replication genes and human disease At least 80 human diseases result from genetic mutations. At least 32 of these diseases result from mutations in genes encoding either DNA replication or repair proteins. Disease Affected Proteins Progressive external ophthalmoplegia (PEO) Mitochondrial DNA polymerase y Alpers syndrome Mitochondrial DNA polymerase Y Progressive extemal ophthaimoplegia(PEO) Mitochondrial DNA helicase Hereditary non-polyposis colorectal cancer Several DNA mismatch repair proteins (HNPCC).or Lynch syndrome Bloom syndrome DNA helicase Wemer syndrome DNA helicase Rothmund-Thomson syndrome DNA helicase Rapadillino Syndrome DNA helicase Xeroderma pigmentosum varant DNA polymerase n XP-Cockayne syndrome DNA helicase Trichothiodystrophy DNAhelicases LIG4 syndrome DNA ligase Miller-Dieker lissencephaly syndrome* Contiguous haploinsufficiency(-20 genes)including the gene for Replication Factor A (single-stranded DNA-binding protein) William Beuren syndrome' Contiguous haploinsuficiency(-24 genes)including the gene for a subunit of Replication Factor C(clamp loader) *syndromes that MAY be related to DNA replication or repair proteins