European Society of Human Genetics (ESHG) Conference, June 6–9, 2015, Glasgow, UK

Patients with adenomatous polyposis have higher risk for colorectal cancer; however causative genes remain unknown in a considerable fraction of these patients. On behalf of his collaborators, Robbert Weren (Nijmegen, Netherlands) presented whole-exome sequencing data from 51 individuals (of 48 families) with adenomatous polyposis. They identified a homozygous germline nonsense mutation in the base-excision repair (BER) gene NTHL1 in 7 affected individuals from 3 unrelated families. These patients were homozygous for the germline mutation, and showed recessive inheritance of the adenomatous polyposis phenotype, whereas in controls, this mutation was only found in a heterozygous state. Thus, this newNTHL1 genemutation predisposes the homozygous individuals to a novel subtype of BERassociated adenomatous polyposis and colorectal cancer.