Germline mutations of the adenomatous polyposis coli (APC) gene in Algerian familial adenomatous polyposis cohort: first report

Background

Familial adenomatous polyposis (known also as classical or severe FAP) is a rare autosomal dominant colorectal cancer predisposition syndrome, characterized by the presence of hundreds to thousands of adenomatous polyps in the colon and rectum from an early age. In the absence of prophylactic surgery, colorectal cancer (CRC) is the inevitable consequence of FAP. The vast majority of FAP is caused by germline mutations in the adenomatous polyposis coli (APC) tumor suppressor gene (5q21). To date, most of the germline mutations in classical FAP result in truncation of the APC protein and 60% are mainly located within exon 15.

Material and methods

In this first nationwide study, we investigated the clinical and genetic features of 52 unrelated Algerian FAP families. We screened by PCR-direct sequencing the entire exon 15 of APC gene in 50 families and two families have been analyzed by NGS using a cancer panel of 30 hereditary cancer genes.

Results

Among 52 FAP index cases, 36 had 100 or more than 100 polyps, 37 had strong family history of FAP, 5 developed desmoids tumors, 15 had extra colonic manifestations and 21 had colorectal cancer. We detected 13 distinct germline mutations in 17 FAP families. Interestingly, 4 novel APC germline pathogenic variants never described before have been identified in our study.

Conclusions

The accumulating knowledge about the prevalence and nature of APC variants in Algerian population will contribute in the near future to the implementation of genetic testing and counseling for FAP patients.

     

Contrasted resistance of stone-dwelling Geodermatophilaceae species to stresses known to give rise to reactive oxygen species

Stones in arid environments are inhabited by actinobacteria of the family Geodermatophilaceae like the genera Blastococcus and Modestobacter frequently isolated from altered calcarenites. Their habitat requires adaptation to light-induced and other stresses that generate reactive oxygen species. Here, we show that representative members of the species Blastococcus saxobsidens, Geodermatophilus obscurus, and Modestobacter multiseptatus are differentially adapted to stresses associated with arid environments. Whereas B.?saxobsidens was found to be sensitive to gamma radiation (D(10) =?900 Gy; 10% survival at 900 Gy), M.?multiseptatus was moderately (D(10) =?6000 Gy) and G.?obscurus was highly tolerant (D(10) =?9000 Gy). A difference in resistance to high-frequency (λ value?=?254?nm) UV was shown by B.?saxobsidens, M.?multiseptatus, and G.?obscurus, being sensitive, tolerant, and highly tolerant (D(10) of 6, 900, and >?3500?kJ?m(-2) , respectively). Tolerance to desiccation, mitomycin C and hydrogen peroxide correlated with the ionizing radiation and UV resistance profiles of the three species and were correlated with the pigments synthesized. Resistance to heavy metals/metalloids did not follow the same pattern, with resistance to Ag(2+) and Pb(2+) being similar for B.?saxobsidens, M.?multiseptatus, and G.?obscurus, whereas resistance to AsO4 3-, Cr(2+) , or Cu(2+) was greater for B.?saxobsidens than for the other two species. The stress resistance profiles of M.?multiseptatus and B.?saxobsidens were reflected in different calcarenite colonization patterns. While M.?multiseptatus was predominantly isolated from the first two millimeters of stone surface, B.?saxobsidens was predominantly isolated from the deeper part of the stone where it is better protected from sun irradiation, suggesting that the response to light- and desiccation-induced oxidative stress is an important driver for niche colonization in the stone biotope.     

Continuous wavelet filtering on webcam photoplethysmographic signals to remotely assess the instantaneous heart rate

Photoplethysmographic signals obtained from a webcam are analyzed through a continuous wavelet transform to assess the instantaneous heart rate. The measurements are performed on human faces. Robust image and signal processing are introduced to overcome drawbacks induced by light and motion artifacts. In addition, the respiration signal is recovered using the heart rate series by respiratory sinus arrhythmia, the natural variation in heart rate driven by the respiration. The presented algorithms are implemented on a mid-range computer and the overall method works in real-time. The performance of the proposed heart and breathing rates assessment method was evaluated using approved contact probes on a set of 12 healthy subjects. Results show high degrees of correlation between physiological measurements even in the presence of motion. This paper provides a motion-tolerant method that remotely measures the instantaneous heart and breathing rates. These parameters are particularly used in telemedicine and affective computing, where the heart rate variability analysis can provide an index of the autonomic nervous system.