Delineating the Phenotypic Spectrum of the NTHL1-Associated Polyposis

A causal association of NTHL1 biallelic mutations with predisposition to colorectal cancer (CRC) and adenomatous polyposis has been recently reported, 1 largely resembling the recessive syndrome caused by MUTYH mutations. 2 NTHL1 [NM_002528] c.268C>T (p.Gln90*) was identified in homozygous state in 3 hereditary cancer and polyposis families. No other mutations were then reported. 1 Subsequently, Rivera et al3 described a biallelic carrier of c.268C>T (p.Gln90*) in combination with c.709_1G> A. The c.268C> T variant (rs150766139) is the most frequent NTHL1 truncating mutation in the population (minor allele frequency [MAF] Exome Aggregation Consortium [MAFExAC], 0.15%) and has higher prevalence in European cohorts (MAFExAC, 0.24%) (http:// exac. broadinstitute. org/). We genotyped c.268C> T in unexplained hereditary nonpolyposis CRC and polyposis patients, to evaluate its relevance and help refine the associated phenotype.