F J Hes

..It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership...

..5% is a heterozygous MUTYH mutation carrier. Children of MAP patients have an increased risk of inheriting two MUTYH mutations compared to the general population, implicating an increased risk for developing CRC...

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..As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer...

..VHL associated tumours are richly vascularised. This is consistent with the involvement of the VHL protein in multiprotein complexes that degrade hypoxia-inducible factors dependent on cellular oxygen levels...

..Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems...

..The patient with 10 or more adenomas in the colon poses a diagnostic challenge. Beside germline mutations in the APC and MUTYH genes, only four cases of mosaic APC mutations have been reported...

..The identification of multiple causes in a single patient may complicate explaining the disorder and genetic counseling...

..Insights into the pathology of rare genetic syndromes may have important lessons for our understanding of much commoner conditions...

..We evaluate the phenotype and penetrance of a germline SDHB mutation in a large and clinically well-characterized paraganglioma family...

..A patient with (suspicion for) VHL is an indication for genetic counselling and periodical examination...

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..The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment...

..The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken...

..In conclusion, these data would support the notion that abrogation of both MSH6 DNA mismatch repair and base repair might be mutually exclusive in humans...

..The tissues were tested for somatic KRAS2 mutations and for three Dutch hotspot MUTYH germ line mutations (p.Tyr165Cys, p.Gly382Asp, and p.Pro391Leu) by sequencing analysis...

..We evaluated the natural history of the disease and the outcome of colorectal surveillance and management...

..The results presented in this study suggest that copy-neutral LOH is an important mechanism in the tumorigenesis of MAP...

..Overall, our results suggest that clustering of low-risk variants may explain part of the excess risk in CRC families...

..We assessed the lifetime risk of benign and malignant gastrointestinal lesions in patients with a proven PTEN mutation...

..Studies in larger series of MAP patients are needed to investigate the risk of upper-gastro-intestinal malignancies and to determine further guidelines for endoscopical surveillance...

..MutYH polyposis differs from familial adenomatous polyposis coli in its mode of transmission, later age of onset, a less florid form of polyposis, and fewer extra colonic manifestations...

..Four of these (21%) are lying in the region with frequent sequence transfer and are missed or called incorrectly as homozygous with several PSV-based mutation detection methods...

..We aimed to identify SDHAF2 mutation carriers, assess the clinical genetic significance of SDHAF2, and describe the associated clinical phenotype...

..We describe custom bioinformatics and statistics to optimize detection of rare variants and to estimate required sequencing depth. Our results provide directions for designing high-throughput analyses of candidate genes...

..While most total and partial APC deletions lead to a classic FAP phenotype, specific (in-frame) deletions may lead to an attenuated polyposis phenotype...

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..Gene deletions of SDHD and SDHC represent a substantial proportion of all mutations, and must be considered in paraganglioma patients shown to be negative for mutations by sequencing...

..Our data provide additional evidence for a link between DNA repair deficiencies and altered HLA class I phenotypes in colorectal cancer...

..We focus on the three most common hereditary colorectal cancer syndromes (CCS): Lynch syndrome, familial adenomatous polyposis and MUTYH-associated polyposis...

..Our goal was to establish correlations between genotypes and colorectal phenotype of patients with MAP...

..This open-access repository allows all involved to quickly share all variants encountered and communicate potential consequences, which will be especially useful to classify variants of uncertain significance...

..To assess whether these influence CRC risk in the Lynch syndrome, we genotyped these variants in a large series of proven mutation carriers...

..The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families...

..The approach we describe here shows to be an excellent way to study genome-wide cnLOH in archival mismatch repair deficient tumors...

..Germline PRKAR1A mutations cause CNC and only rarely isolated PPNAD...

..002) and the published controls (P = 0.001). These results warrant further study to test the hypothesis of mutations in MMR genes (in particular MSH6) and MUTYH acting together to increase cancer risk...

..Finally, we have investigated the frequency of both deletions using a random Belgian cohort. Given the global occurrence, HCS should be considered in the differential diagnosis of neonatal hypotonia...