Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families

<p>Abstract</p> <p>Background</p> <p>The dominantly inherited condition familial adenomatous polyposis (FAP) is caused by germline mutations in the <it>APC </it>gene. Finding the causative mutations has great implications for the families. Correlating the genotypes to the phenotypes could help to improve the diagnosis and follow-up of patients.</p> <p>Methods</p> <p>Mutation screening of <it>APC </it>and the clinical characterization of 96 unrelated FAP patients from the Swedish Polyposis Registry was performed. In addition to generally used mutation screening methods, analyses of splicing-affecting mutations and investigations of the presence of low-frequency mutation alleles, indicating mosaics, have been performed, as well as quantitative real-time polymerase chain reaction to detect lowered expression of <it>APC</it>.</p> <p>Results</p> <p>Sixty-one different <it>APC </it>mutations in 81 of the 96 families were identified and 27 of those are novel. We have previously shown that 6 of the 96 patients carried biallelic <it>MUTYH </it>mutations. The 9 mutation-negative cases all display an attenuated or atypical phenotype. Probands with a genotype (codon 1250–1464) predicting a severe phenotype had a median age at diagnosis of 21.8 (range, 11–49) years compared with 34.4 (range, 14–57) years among those with mutations outside this region (<it>P </it>< 0.017). Dense polyposis (> 1000) occurred in 75% of the probands with a severe phenotype compared with 30% in those with mutations outside this region. The morbidity in colorectal cancer among probands was 25% at a mean age of 37.5 years and 29% at a mean age of 46.6 years.</p> <p>Conclusion</p> <p>Using a variety of mutation-detection techniques, we have achieved a 100% detection frequency in classical FAP. Probands with <it>APC </it>mutations outside codon 1250–1464, although exhibiting a less-severe phenotype, are at high risk of having a colorectal cancer at diagnosis indicating that age at diagnosis is as important as the severity of the disease for colorectal cancer morbidity.</p

Physical properties of the trans-Neptunian object (38628) Huya from a multi-chord stellar occultation

Within our international program to obtain accurate physical properties of trans-Neptunian objects (TNOs) we predicted a stellar occultation by the TNO (38628) Huya of the star Gaia DR2 4352760586390566400 (mG = 11.5 mag.) for March 18, 2019. After an extensive observational campaign, we updated the prediction and it turned out to be favorable to central Europe. Therefore, we mobilized half a hundred professional and amateur astronomers, and the occultation was finally detected from 21 telescopes located at 18 sites. This makes the Huya event one of the best ever observed stellar occultation by a TNO in terms of the number of chords. We determine accurate size, shape, and geometric albedo, and we also provide constraints on the density and other internal properties of this TNO. The 21 positive detections of the occultation by Huya allowed us to obtain well-separated chords which permitted us to fit an ellipse for the limb of the body at the moment of the occultation (i.e., the instantaneous limb) with kilometric accuracy. The projected semi-major and minor axes of the best ellipse fit obtained using the occultation data are (a', b') = (217.6 $\pm$ 3.5 km, 194.1 $\pm$ 6.1 km) with a position angle of the minor axis P' = 55.2 $\pm$ 9.1 degrees. From this fit, the projected area-equivalent diameter is 411.0 $\pm$ 7.3 km. This diameter is compatible with the equivalent diameter for Huya obtained from radiometric techniques (D = 406 $\pm$ 16 km). From this instantaneous limb, we obtained the geometric albedo for Huya (p$\rm_V$ = 0.079 $\pm$ 0.004) and we explored possible 3D shapes and constraints to the mass density for this TNO. We did not detect the satellite of Huya through this occultation, but the presence of rings or debris around Huya is constrained using the occultation data. We also derived an upper limit for a putative Pluto-like global atmosphere of about p$_{\rm surf}$ = 10 nbar.Comment: Accepted for publication in Astronomy & Astrophysics (30-April-2022). 19 pages, 7 figure