Identification of a mutL-homolog 1 mutation via whole-exome sequencing in a Chinese family with Gardner syndrome

摘要

Gardner syndrome (GS), a variant of familial adenomatous polyposis, is a rare genetic disorder with autosomal dominant inheritance, characterized by the presence of multiple intestinal polyps, multiple osteomas, dental abnormalities and soft tissue tumors. To date, only a few gene mutations have been demonstrated to be responsible for GS. To explore potential unknown mutations responsible for GS, the present study used whole-exome sequencing of two affected individuals from a family with GS to identify a candidate mutation in mutL-homolog (MLH)1. The two patients with GS were diagnosed based on a combination of clinical features, family history, physical examinations and cone-beam computed tomographic imaging. Through whole-genome sequencing, the present study subsequently identified a missense mutation in MLH1 (NM_000249.3:p.Tyr379Seric.1136AC), which was further confirmed by Sanger sequencing. Furthermore, the amino acid residue p.Tyr379 was identified to be highly conserved among different species through sequence alignment with ClustalW2. In conclusion, the results identified for the first time a MLH1 missense mutation (N _000249.3: p.Tyr379Seric.1136AC) in a Chinese family with GS, thus broadening the range of mutated genes associated with GS. This highlights the value of whole-exome sequencing in identifying disease mutations in a family.