Since the number of patients with DC is small and the effect of genetic pathogenic variant may affect the phenotype, we wanted to present the clinical features and course of illness in a patient with NHP2 gene mutation (compound heterozygote for the NHP2 mutations c.376G>A/c.460T>A; amino acid substitutions: p.Val126Met and p.X154Arg) that occurred as a compound heterozygous state.
We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (n = 3 BAP1, n = 15 MITF p.E318K; diagnostic yield 4.0%).
Functional experiments were used to further clarify the potential function of the significant variant and uncover the underlying mechanism in colorectal cancer development.<b>Results:</b> The two-stage association studies showed that a rare missense variant rs149418249 (c.<i>C</i>1520<i>T</i> and p.P507L) in the 11th exon of <i>TPP1</i> (also known as <i>ACD</i>, gene ID 65057) was significantly associated with colorectal cancer risk with the ORs being 2.90 [95% confidence interval (CI), 1.04-8.07; <i>P</i> = 0.041], 2.50 (95% CI, 1.04-6.04; <i>P</i> = 0.042), and 2.66 (95% CI, 1.36-5.18; <i>P</i> = 0.004) in discovery, replication, and the combined samples, respectively.
Functional experiments were used to further clarify the potential function of the significant variant and uncover the underlying mechanism in colorectal cancer development.<b>Results:</b> The two-stage association studies showed that a rare missense variant rs149418249 (c.<i>C</i>1520<i>T</i> and p.P507L) in the 11th exon of <i>TPP1</i> (also known as <i>ACD</i>, gene ID 65057) was significantly associated with colorectal cancer risk with the ORs being 2.90 [95% confidence interval (CI), 1.04-8.07; <i>P</i> = 0.041], 2.50 (95% CI, 1.04-6.04; <i>P</i> = 0.042), and 2.66 (95% CI, 1.36-5.18; <i>P</i> = 0.004) in discovery, replication, and the combined samples, respectively.
Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively.