Simple Summary: Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes may raise awareness and assist clinicians in the diagnosis and interpretation of... Show moreSimple Summary: Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes may raise awareness and assist clinicians in the diagnosis and interpretation of molecular test results. Genetic predisposition to colorectal cancer (CRC) should be suspected mainly in young patients, in patients with significant family histories, multiple polyps, mismatch repair-deficient tumors, and in association with malignant or nonmalignant comorbidities. The aim of this review is to describe the main nonmalignant comorbidities associated with selected CRC predisposition syndromes that may serve as valuable diagnostic clues for clinicians and genetic professionals.& nbsp;Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-beta, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation. Show less
Iacomelli, I.; Barberio, G.; Pucci, P.; Monaco, V.; Maffei, M.; Mogni, M.; ... ; Ivaldi, G. 2021
Objectives: Artifactually altered glycated hemoglobin (HbA(1c)) concentrations are frequently linked to hemoglobin (Hb) variants. Their expression and detection require in-depth analysis.Methods:... Show moreObjectives: Artifactually altered glycated hemoglobin (HbA(1c)) concentrations are frequently linked to hemoglobin (Hb) variants. Their expression and detection require in-depth analysis.Methods: Cation exchange high performance liquid chromatography (HPLC) (Bio-Rad Variant (TM) II; Trinity Biotech Premier Hb9210 Resolution), capillary electrophoresis (CE) (Sebia Capillarys 2 Flex Piercing) and mass spectrometry (MS) (Waters) were used for variant detection; Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) were used for DNA analysis; HbA(1c) was measured with cation exchange HPLC (Bio-Rad Variant (TM) II; Arkray Adams HA-8180V; Tosoh HLC-723 G7), CE (Sebia Capillarys 2 Flex Piercing), boronate affinity HPLC (Trinity Biotech Hb9210 Premier), immunoassay (Cobas c501 Tina-quant HbA(1c) Gen. 3; Nihon Kohden CHM-4100 Celltac chemi HbA(1c) HA-411V) and enzymatic assay (Abbott Architect c 8000 HbA(1c)).Results: Hb Yamagata [beta 132(H10)Lys -> Asn; (HBB: c.399A>T)] was identified in the proband by MS after the observation of an abnormal peak in HPLC and CE. A mosaic expression of this variant was detected by NGS (mutant: 8%; wild type: 92%), after negative results in Sanger sequencing. Hb Yamagata interfered with HbA(1c) measurements by cation exchange HPLC and CE whereas immuno and enzymatic assay values showed good agreement with boronate affinity HPLC measurement.Conclusions: A mosaicism of Hb Yamagata was found in a patient with altered HbA(1c) values. This rare gene variant was detected only by advanced technologies as MS and NGS. The variant interfered with common HbA(1c) determination methods. Show less
![Hemoglobin Yamagata [beta 132(H10)Lys -> Asn; (HBB: c.399A > T)]: a mosaic to be put together](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=5eb982efea4ef4b06bef&solr_nav%5Bpage%5D=0&solr_nav%5Boffset%5D=1)
