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  • 1
    Language: English
    In: International journal of cancer, 2015-07-15, Vol.137 (2), p.320-331
    Description: In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome/HNPCC, no germline alteration in the APC, MUTYH, or mismatch repair (MMR) genes are found. Missense mutations in the polymerase genes POLE and POLD1 have recently been identified as rare cause of multiple colorectal adenomas and carcinomas, a condition termed polymerase proofreading‐associated polyposis (PPAP). The aim of the present study was to evaluate the clinical relevance and phenotypic spectrum of polymerase germline mutations. Therefore, targeted sequencing of the polymerase genes POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3 and POLE4 was performed in 266 unrelated patients with polyposis or fulfilled Amsterdam criteria. The POLE mutation c.1270C〉G;p.Leu424Val was detected in four unrelated patients. The mutation was present in 1.5% (4/266) of all patients, 4% (3/77) of all familial cases and 7% (2/30) of familial polyposis cases. The colorectal phenotype in 14 affected individuals ranged from typical adenomatous polyposis to a HNPCC phenotype, with high intrafamilial variability. Multiple colorectal carcinomas and duodenal adenomas were common, and one case of duodenal carcinoma was reported. Additionally, various extraintestinal lesions were evident. Nine further putative pathogenic variants were identified. The most promising was c.1306C〉T;p.Pro436Ser in POLE. In conclusion, a PPAP was identified in a substantial number of polyposis and familial colorectal cancer patients. Screening for polymerase proofreading mutations should therefore be considered, particularly in unexplained familial cases. The present study broadens the phenotypic spectrum of PPAP to duodenal adenomas and carcinomas, and identified novel, potentially pathogenic variants in four polymerase genes. What's New? A substantial number of families with adenomatous polyposis and Lynch‐like phenotype have no known underlying germline mutations. Recently new mutations in the genes encoding DNA polymerase epsilon and delta were identified. Here the authors characterize the frequency and phenotypic spectrum of this newly described polymerase proofreading‐associated polyposis (PPAP) syndrome. They broadened the tumor spectrum to duodenal neoplasias, extraintestinal tumors and multiple colorectal carcinomas, underscoring the clinical relevance of this syndrome beyond adenomatous polyposis. In addition, they identified nine novel, potentially pathogenic variants in four polymerase genes.
    Subject(s): adenomatous polyposis ; next‐generation sequencing ; familial colorectal cancer ; gastrointestinal polyposis syndromes ; Lynch syndrome ; Adenoma - genetics ; Colorectal Neoplasms - genetics ; Humans ; Middle Aged ; Family Health ; Male ; Mutation, Missense ; DNA-Directed DNA Polymerase - genetics ; Young Adult ; Poly-ADP-Ribose Binding Proteins ; Adenoma - enzymology ; Aged, 80 and over ; Germ-Line Mutation ; Adult ; Female ; Phospholipase D - genetics ; Child ; DNA Polymerase II - genetics ; Colorectal Neoplasms - enzymology ; Genetic Predisposition to Disease - genetics ; Isoenzymes - genetics ; Gene Frequency ; Phenotype ; Pedigree ; Adolescent ; Aged ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA - methods ; Gene mutations ; Genes ; Colorectal cancer ; Genetic research ; Genetic aspects ; Diagnosis ; Cancer ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Human mutation, 2020-05, Vol.41 (5), p.1025-1032
    Description: As comprehensive sequencing technologies gain widespread use, questions about so‐called secondary findings (SF) require urgent consideration. The American College of Medical Genetics and Genomics has recommended to report SF in 59 genes (ACMG SF v2.0) including four actionable genes associated with inherited primary arrhythmia syndromes (IPAS) such as catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, and Brugada syndrome. Databases provide conflicting results for the purpose of identifying pathogenic variants in SF associated with IPAS at a level of sufficient evidence for clinical return. As IPAS account for a significant proportion of sudden cardiac deaths (SCD) in young and apparently healthy individuals, variant interpretation has a great impact on diagnosis and prevention of disease. Of 6381 individuals, 0.4% carry pathogenic variants in one of the four actionable genes related to IPAS: RYR2, KCNQ1, KCNH2, and SCN5A. Comparison of the databases ClinVar, Leiden Open‐source Variant Database, and Human Gene Mutation Database showed impactful differences (0.2% to 1.3%) in variant interpretation improvable by expert‐curation depending on database and classification system used. These data further highlight the need for international consensus regarding the variant interpretation, and subsequently management of SF in particular with regard to treatable arrhythmic disorders with increased risk of SCD. We critically assessed secondary findings (SF) in actionable genes (RYR2, KCNQ1, KCNH2, and SCN5A) linked to inherited primary arrhythmia syndromes. Comparison of the databases showed impactful differences in variant interpretation. The study highlights the need of international consensus regarding the variant interpretation, and subsequently management of SF in particular with regard to treatable arrhythmia disorders with increased risk of sudden cardiac death.
    Subject(s): variant classification ; cardiac channelopathy genes ; secondary findings ; actionable genes ; primary arrhythmia syndromes ; variant interpretation ; Index Medicus
    ISSN: 1059-7794
    E-ISSN: 1098-1004
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: International journal of cancer, 2021-01-01, Vol.148 (1), p.106-114
    Description: In our study, we evaluated the effectiveness of upper gastrointestinal (GI) endoscopy as an instrument for early gastric cancer (GC) detection in Lynch syndrome (LS) patients by analyzing data from the registry of the German Consortium for Familial Intestinal Cancer. In a prospective, multicenter cohort study, 1128 out of 2009 registered individuals with confirmed LS underwent 5176 upper GI endoscopies. Compliance was good since 77.6% of upper GI endoscopies were completed within the recommended interval of 1 to 3 years. Forty‐nine GC events were observed in 47 patients. MLH1 (n = 21) and MSH2 (n = 24) mutations were the most prevalent. GCs in patients undergoing regular surveillance were diagnosed significantly more often in an early‐stage disease (UICC I) than GCs detected through symptoms (83% vs 25%; P = .0231). Thirty‐two (68%) patients had a negative family history of GC. The median age at diagnosis was 51 years (range 28‐66). Of all GC patients, 13 were diagnosed at an age younger than 45. Our study supports the recommendation of regular upper GI endoscopy surveillance for LS patients beginning no later than at the age of 30. What's new? Risk of gastric cancer (GC) is significantly increased among patients with Lynch syndrome (LS). GC screening in LS patients, however, is fraught with uncertainty, particularly regarding the use of esophagogastroduodenoscopy (EGD). The authors of this study investigated the use of EGD for regular GC surveillance in a German cohort of LS patients. Regular surveillance by EGD resulted in more frequent diagnosis and significant down‐staging of GC, relative to detection via symptoms alone. In most cases, family history of GC was negative. This study supports recommendations for regular gastroscopic surveillance in LS patients starting by age 30.
    Subject(s): HNPCC ; screening ; surveillance ; gastric cancer ; Lynch syndrome ; Care and treatment ; Cancer patients ; Oncology, Experimental ; Analysis ; Research ; Diagnosis ; Endoscopy ; Stomach cancer ; Cancer ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Human mutation, 2012-07, Vol.33 (7), p.1045-1050
    Description: To uncover pathogenic deep intronic variants in patients with colorectal adenomatous polyposis, in whom no germline mutation in the APC or MUTYH genes can be identified by routine diagnostics, we performed a systematic APC messenger RNA analysis in 125 unrelated mutation‐negative cases. Overall, we identified aberrant transcripts in 8% of the patients (familial cases 30%; early‐onset manifestation 21%). In eight of them, two different out‐of‐frame pseudoexons were found consisting of a 167‐bp insertion from intron 4 in five families with a shared founder haplotype and a 83‐bp insertion from intron 10 in three patients. The pseudoexon formation was caused by three different heterozygous germline mutations, which are supposed to activate cryptic splice sites. In conclusion, a few deep intronic mutations contribute substantially to the APC mutation spectrum. Complementary DNA analysis and/or target sequencing of intronic regions should be considered as an additional mutation discovery approach in polyposis patients. Hum Mutat 33:1045–1050, 2012. © 2012 Wiley Periodicals, Inc.
    Subject(s): aberrant splicing ; APC ; familial adenomatous polyposis ; exon skipping ; pseudoexons ; Adenomatous Polyposis Coli Protein - genetics ; Genetic Predisposition to Disease - genetics ; Introns - genetics ; Mutation ; Adenomatous Polyposis Coli - genetics ; Humans ; Index Medicus
    ISSN: 1059-7794
    E-ISSN: 1098-1004
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Journal of inherited metabolic disease, 2016-05, Vol.39 (3), p.427-436
    Description: Liver failure is a heterogeneous condition which may be fatal and the primary cause is frequently unknown. We investigated mitochondrial oxidative phosphorylation in patients undergoing liver transplantation. We studied 45 patients who had liver transplantation due to a variety of clinical presentations. Blue native polyacrylamide gel electrophoresis with immunodetection of respiratory chain complexes I-V, biochemical activity of respiratory chain complexes II and IV and quantification of mitochondrial DNA (mtDNA) copy number were investigated in liver tissue collected from the explanted liver during transplantation. Abnormal mitochondrial function was frequently present in this cohort: ten of 40 patients (25 %) had a defect of one or more respiratory chain enzyme complexes on blue native gels, 20 patients (44 %) had low activity of complex II and/or IV and ten (22 %) had a reduced mtDNA copy number. Combined respiratory chain deficiency and reduced numbers of mitochondria were detected in all three patients with acute liver failure. Low complex IV activity in biliary atresia and complex II defects in cirrhosis were common findings. All six patients diagnosed with liver tumours showed variable alterations in mitochondrial function, probably due to the heterogeneity of the presenting tumour. In conclusion, mitochondrial dysfunction is common in severe liver failure in non-mitochondrial conditions. Therefore, in contrast to the common practice detection of respiratory chain abnormalities in liver should not restrict the inclusion of patients for liver transplantation. Furthermore, improving mitochondrial function may be targeted as part of a complex therapy approach in different forms of liver diseases.
    Subject(s): Human Genetics ; Biochemistry, general ; Pediatrics ; Internal Medicine ; Medicine & Public Health ; Metabolic Diseases ; Mitochondrial Diseases - pathology ; Liver - pathology ; Humans ; Middle Aged ; Mitochondrial Diseases - metabolism ; Child, Preschool ; Liver Failure - pathology ; Infant ; Male ; Electron Transport Complex IV - metabolism ; Young Adult ; Liver Failure - metabolism ; Liver Transplantation - methods ; Liver Cirrhosis - metabolism ; Adult ; Female ; Liver Neoplasms - pathology ; Electron Transport - physiology ; Child ; DNA, Mitochondrial - metabolism ; Liver - metabolism ; Oxidative Phosphorylation ; Mitochondria - metabolism ; Mitochondria - pathology ; Biliary Atresia - metabolism ; Biliary Atresia - pathology ; Adolescent ; Liver Neoplasms - metabolism ; Liver Cirrhosis - pathology ; Enzymes ; Liver failure ; Transplantation ; Mitochondrial DNA ; Liver cirrhosis ; Liver ; Index Medicus ; Original
    ISSN: 0141-8955
    E-ISSN: 1573-2665
    Source: Wiley Online Library All Journals
    Source: EBSCOhost EJS
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: International journal of cancer, 2017-10-01, Vol.141 (7), p.1365-1380
    Description: In a proportion of patients presenting mismatch repair (MMR)-deficient tumors, no germline MMR mutations are identified, the so-called Lynch-like syndrome (LLS). Recently, MMR-deficient tumors have been associated with germline mutations in POLE and MUTYH or double somatic MMR events. Our aim was to elucidate the molecular basis of MSH2-deficient LS-suspected cases using a comprehensive analysis of colorectal cancer (CRC)-associated genes at germline and somatic level. Fifty-eight probands harboring MSH2-deficient tumors were included. Germline mutational analysis of MSH2 (including EPCAM deletions) and MSH6 was performed. Pathogenicity of MSH2 variants was assessed by RNA analysis and multifactorial likelihood calculations. MSH2 cDNA and methylation of MSH2 and MSH6 promoters were studied. Matched blood and tumor DNA were analyzed using a customized next generation sequencing panel. Thirty-five individuals were carriers of pathogenic or probably pathogenic variants in MSH2 and EPCAM. Five patients harbored 4 different MSH2 variants of unknown significance (VUS) and one had 2 novel MSH6 promoter VUS. Pathogenicity assessment allowed the reclassification of the 4 MSH2 VUS and 6 probably pathogenic variants as pathogenic mutations, enabling a total of 40 LS diagnostics. Predicted pathogenic germline variants in BUB1, SETD2, FAN1 and MUTYH were identified in 5 cases. Three patients had double somatic hits in MSH2 or MSH6, and another 2 had somatic alterations in other MMR genes and/or proofreading polymerases. In conclusion, our comprehensive strategy combining germline and somatic mutational status of CRC-associated genes by means of a subexome panel allows the elucidation of up to 86% of MSH2-deficient suspected LS tumors.
    Subject(s): Histone-Lysine N-Methyltransferase - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Humans ; DNA Glycosylases - genetics ; Protein-Serine-Threonine Kinases - genetics ; Multifunctional Enzymes ; MutS Homolog 2 Protein - genetics ; DNA Mismatch Repair - genetics ; DNA-Binding Proteins - genetics ; Loss of Heterozygosity ; Promoter Regions, Genetic - genetics ; DNA-Binding Proteins - deficiency ; Endodeoxyribonucleases ; DNA Methylation ; DNA Mutational Analysis ; MutS Homolog 2 Protein - deficiency ; Epithelial Cell Adhesion Molecule - genetics ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Exodeoxyribonucleases - genetics ; Gene mutations ; Methylation ; Analysis ; Colorectal cancer ; Tumors ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: International journal of cancer, 2015-03-15, Vol.136 (6), p.E578-E589
    Description: To uncover novel causative genes in patients with unexplained adenomatous polyposis, a model disease for colorectal cancer, we performed a genome‐wide analysis of germline copy number variants (CNV) in a large, well characterized APC and MUTYH mutation negative patient cohort followed by a targeted next generation sequencing (NGS) approach. Genomic DNA from 221 unrelated German patients was genotyped on high‐resolution SNP arrays. Putative CNVs were filtered according to stringent criteria, compared with those of 531 population‐based German controls, and validated by qPCR. Candidate genes were prioritized using in silico, expression, and segregation analyses, data mining and enrichment analyses of genes and pathways. In 27% of the 221 unrelated patients, a total of 77 protein coding genes displayed rare, nonrecurrent, germline CNVs. The set included 26 candidates with molecular and cellular functions related to tumorigenesis. Targeted high‐throughput sequencing found truncating point mutations in 12% (10/77) of the prioritized genes. No clear evidence was found for autosomal recessive subtypes. Six patients had potentially causative mutations in more than one of the 26 genes. Combined with data from recent studies of early‐onset colorectal and breast cancer, recurrent potential loss‐of‐function alterations were detected in CNTN6, FOCAD (KIAA1797), HSPH1, KIF26B, MCM3AP, YBEY and in three genes from the ARHGAP family. In the canonical Wnt pathway oncogene CTNNB1 (β‐catenin), two potential gain‐of‐function mutations were found. In conclusion, the present study identified a group of rarely affected genes which are likely to predispose to colorectal adenoma formation and confirmed previously published candidates for tumor predisposition as etiologically relevant. What's new? So far, two genes have been implicated in the inheritance of adenomatous polyposis, a condition that leads to colorectal cancer: APC and MAP. But disturbances in these genes only account for about half of the disease cases. In this study, the authors sought that genetic basis by performing for the first time a genome‐wide investigation into copy number variations among colorectal adenomatous polyposis patients. They identified a group of candidate genes that boost the risk of hereditary colorectal tumors; several patients had disruptions in multiple genes, suggesting that a simple lab test to evaluate risk might not be forthcoming.
    Subject(s): copy number variation ; candidate genes ; next generation sequencing ; unexplained polyposis ; gastrointestinal polyposis ; genetic cause ; hereditary colorectal cancer ; Genome-Wide Association Study ; Humans ; Middle Aged ; DNA Glycosylases - genetics ; Protein-Serine-Threonine Kinases - genetics ; beta Catenin - genetics ; DNA Copy Number Variations ; HSP110 Heat-Shock Proteins - genetics ; Adolescent ; Kinesin - genetics ; Adult ; Aged ; High-Throughput Nucleotide Sequencing ; Adenomatous Polyposis Coli - genetics ; Child ; Intracellular Signaling Peptides and Proteins - genetics ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: International journal of cancer, 2014-07-01, Vol.135 (1), p.69-77
    Description: Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive and time‐consuming, clinical criteria and tumor‐tissue analysis are widely used as pre‐screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumor‐tissue analysis in predicting MMR gene mutations. We analyzed 3,671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mutation. Among all 1,284 families with microsatellite instability‐high (MSI‐H) colorectal cancer, the overall mutation detection rate was 53.0%. Mutation frequencies and their distribution between the four MMR genes differed significantly between clinical groups (p 〈 0.001). The highest frequencies were found in families fulfilling the Amsterdam Criteria (46.4%). Families with loss of MSH2 expression had higher mutation detection rates (69.5%) than families with loss of MLH1 expression (43.1%). MMR mutations were found significantly more often in families with at least one MSI‐H small‐bowel cancer (p 〈 0.001). No MMR mutations were found among patients under 40‐years‐old with only colorectal adenoma. Familial clustering of Lynch syndrome‐related tumors, early age of onset, and familial occurrence of small‐bowel cancer were clinically relevant predictors for Lynch syndrome. What's new? Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for a wide range of malignancies—an autosomal‐dominant genetic condition that is known as Lynch syndrome. As mutation analysis to detect these patients is expensive and time‐consuming, clinical criteria are widely used for pre‐screening. Only a few studies have however been conducted to investigate the predictive performance of such clinical criteria. This larger study identified familial clustering of Lynch syndrome‐related tumours, early age of onset, and familial occurrence of small‐bowel cancer as relevant predictors, which may assist clinicians in proving the existence of Lynch syndrome in a family.
    Subject(s): HNPCC ; mismatch‐repair defects ; clinical diagnostic criteria ; lynch syndrome ; Bethesda guidelines ; Gastroenterology. Liver. Pancreas. Abdomen ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Biological and medical sciences ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Medical sciences ; Tumors ; MutL Protein Homolog 1 ; Microsatellite Instability ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology ; Humans ; Middle Aged ; DNA Repair Enzymes - genetics ; Male ; MutS Homolog 2 Protein - genetics ; DNA Mismatch Repair - genetics ; DNA-Binding Proteins - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis ; DNA Mutational Analysis ; Adaptor Proteins, Signal Transducing - genetics ; Germ-Line Mutation ; Adult ; Female ; Adenosine Triphosphatases - genetics ; Aged ; Mismatch Repair Endonuclease PMS2 ; Nuclear Proteins - genetics ; Medical research ; Gene mutations ; Genes ; Colorectal cancer ; Genetic research ; Medicine, Experimental ; Genetic aspects ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: International journal of cancer, 2014-02-15, Vol.134 (4), p.939-947
    Description: Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy were analyzed. One thousand five hundred eighty‐five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient‐years of follow‐up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high‐risk adenomas and 225 (14.2%) simple adenomas. One thousand eighty‐eight individuals had a further colonoscopy (median follow‐up of 6.2 years). Of nine individuals diagnosed with cancer, eight had a previous history of at least one polyp/adenoma. High‐risk adenomas were detected in 92 (8.7%) and multiple adenomas were detected in 20 (1.9%) individuals. Both FCC type X and LOFCC have a high prevalence of colorectal cancers and on follow‐up develop high‐risk adenomas (including multiple adenomas), but infrequent interval cancers. They should be managed similarly with five‐yearly colonoscopies undertaken from between 30 and 40 with more intensive surveillance in individuals developing multiple or high‐risk adenomas. What's new? About 3‐5 percent of colorectal cancer cases are associated with a highly penetrant dominant inherited syndrome. However, established guidelines for the surveillance of Familial Colorectal Cancer (FCC), in which the Polyposis syndromes and Lynch syndrome have been excluded, are lacking. This study suggests that FCC and late‐onset FCC (LOFCC) patients should be managed with five‐yearly colonoscopies between ages 30 and 40, with more intensive surveillance in individuals who develop multiple or high‐risk adenomas. Little evidence was found to support intensive screening before age 30.
    Subject(s): colonoscopic surveillance ; pooled analysis ; Amsterdam criteria ; familial colorectal cancer type X ; Gastroenterology. Liver. Pancreas. Abdomen ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Biological and medical sciences ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Medical sciences ; Tumors ; Colorectal Neoplasms - epidemiology ; Adenoma - diagnosis ; Genetic Predisposition to Disease ; Prognosis ; Prospective Studies ; Follow-Up Studies ; Adenoma - epidemiology ; Humans ; Middle Aged ; Europe - epidemiology ; Male ; Colorectal Neoplasms - diagnosis ; Colonoscopy ; Aged, 80 and over ; Adult ; Female ; Aged ; Neoplasm Staging ; Population Surveillance ; Analysis ; Genetic aspects ; Colorectal cancer ; Index Medicus ; Medicin och hälsovetenskap
    ISSN: 0020-7136
    ISSN: 1097-0215
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Journal of inherited metabolic disease, 2011-02, Vol.34 (1), p.197-201
    Description: Combined respiratory chain deficiency accounts for about 30% of mitochondrial respiratory chain deficiencies and is frequently associated with mtDNA depletion, deletions or point mutations. However combined respiratory chain deficiency may also be caused by mutations in nuclear genes affecting mitochondrial translation. Here we describe a 2-year-old girl, who developed an acute, isolated, severe liver failure with mitochondrial pathology and decreased respiratory chain enzyme activities both in liver and skeletal muscle at 4 months of age. Her liver function improved significantly within a month, liver function tests returned to normal. Liver cirrhosis remained without any further complications so far. Pathogenic compound heterozygous mutations were identified in the TRMU gene. This condition is one of the few mitochondrial disorders with a life-threatening onset showing recovery later in life, therefore a prompt diagnosis and treatment of these patients has great importance in clinical practice. We suggest that TRMU deficiency should be considered in infants with acute liver disease.
    Subject(s): Biochemistry, general ; Human Genetics ; Pediatrics ; Internal Medicine ; Medicine & Public Health ; Metabolic Diseases ; Gastroenterology. Liver. Pancreas. Abdomen ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical genetics ; Biological and medical sciences ; Metabolic diseases ; Medical sciences ; Other diseases. Semiology ; Mitochondrial Diseases - genetics ; Liver Cirrhosis - etiology ; Liver Cirrhosis - diagnosis ; Liver Failure, Acute - complications ; Humans ; Child, Preschool ; Liver Failure, Acute - diagnosis ; Molecular Sequence Data ; Mitochondrial Proteins - genetics ; Mitochondrial Diseases - complications ; Mutation - physiology ; tRNA Methyltransferases - genetics ; Liver Failure, Acute - genetics ; Base Sequence ; Female ; Liver Cirrhosis - genetics ; Mitochondrial Diseases - diagnosis ; Enzymes ; Liver failure ; Gene mutations ; Genetic aspects ; Mitochondrial DNA ; Infants ; Liver cirrhosis ; Index Medicus
    ISSN: 0141-8955
    E-ISSN: 1573-2665
    Source: Wiley Online Library All Journals
    Source: EBSCOhost EJS
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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