Colorectal Cancer Outcomes in a Large Negative Computed Tomography Colonography Screening Cohort.

INTRODUCTION: At our institution, the most common cohort of individuals having computed tomography colonography (CTC) are those that require primary screening for colorectal cancer and were unable to tolerate or failed optical colonoscopy (OC). CTC is an efficient method for detecting polyps, masses, flat-lesions, and overt colorectal cancer, serving as a viable alternative to colonoscopy. This study follows patients with negative CTC results to evaluate the number of clinically significant lesions that may have been potentially missed by CTC. We suspect this number will be exceedingly low given the high sensitivity of this technique. METHODS: All patients with negative CTC screening (n = 509) in the Eastern Health Medical Health Region, located in Newfoundland and Labrador, Canada were included. An electronic medical record review was undertaken, encompassing provider, colonoscopy, imaging, and histopathology reports. Subjects were also checked through the Newfoundland Cancer Clinic Registry Database. All incidents of colorectal cancer were recorded. RESULTS: The study cohort comprised 509 subjects. These subjects were followed for an average of 7.88 years. Two colorectal adenocarcinomas in this cohort were identified representing a crude cancer incidence rate of 0.49 cancers per 1000 patient years, and a rate of 0.39% following a normal CTC. CONCLUSIONS: Colorectal cancer presenting clinically is rare in the 7.88 years following a negative CTC, suggesting CTC is equally effective for colorectal screening compared to OC. Furthermore, current guidelines that recommend interval CTC screening every 5 years is conservative, and interval screening can likely be recommended over a longer time frame.

Identification of a novel in-frame deletion in KCNQ4 (DFNA2A) and evidence of multiple phenocopies of unknown origin in a family with ADSNHL.

Autosomal dominant sensorineural hearing loss (ADSNHL) is extremely genetically heterogeneous, making it difficult to molecularly diagnose. We identified a multiplex (n=28 affected) family from the genetic isolate of Newfoundland, Canada with variable SNHL and used a targeted sequencing approach based on population-specific alleles in WFS1, TMPRSS3 and PCDH15; recurrent mutations in GJB2 and GJB6; and frequently mutated exons of KCNQ4, COCH and TECTA. We identified a novel, in-frame deletion (c.806_808delCCT: p.S269del) in the voltage-gated potassium channel KCNQ4 (DFNA2), which in silico modeling predicts to disrupt multimerization of KCNQ4 subunits. Surprisingly, 10/23 deaf relatives are non-carriers of p.S269del. Further molecular characterization of the DFNA2 locus in deletion carriers ruled out the possibility of a pathogenic mutation other than p.S269del at the DFNA2A/B locus and linkage analysis showed significant linkage to DFNA2 (maximum LOD=3.3). Further support of genetic heterogeneity in family 2071 was revealed by comparisons of audio profiles between p.S269del carriers and non-carriers suggesting additional and as yet unknown etiologies. We discuss the serious implications that genetic heterogeneity, in this case observed within a single family, has on molecular diagnostics and genetic counseling.