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Molecular Screening (molecular + screening)
Selected AbstractsNeurofibromatosis type 1: should we screen for other genetic syndromes?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2009A case report of co-existence with multiple endocrine neoplasia 2A Abstract Background, NF 1 is a genetic disorder with an autosomal dominant pattern of inheritence. It is associated with neoplastic disorders mainly derived from the neural seath. However, the co-existence of NF1 with the full spectrum of MEN 2A has rarely been reported. The aim of the study was to investigate the presence of secondary neoplasias in a patient with diagnosed NF1, and in particular the presence of hyperparathyroidism and the possible co-existence with another pheochromocytoma-related syndrome. Methods, We report a case of a 70 years old female patient who had NF1. The patient was referred to our center and was diagnosed with an isolated pheochromocytoma of the right adrenal gland for which she underwent right adrenalectomy. We further investigated for the presence of another pheochromocytoma-related syndrome and in particular for the presence of hyperparathyroidism and medullary thyroid cancer. Molecular screening for germline mutations of the genes NF1, RET and VHL has also been performed. Results, The patient was further diagnosed with hyperparathyroidism and medullary thyroid cancer, having the full spectrum of the clinical picture of the MEN2A syndrome. The genetic testing revealed the germline mutation for NF1 but not for the RET proto-oncogene which is generally found in MEN2A cases. Conclusion, To our knowledge this is a rare case of co-existence of two pheochromocytoma-related genetic syndromes, and generates the question of whether all patients with these syndromes should undergo a thorough clinical and laboratory investigation for the possibility of another co-existing pheochromocytoma-related genetic syndrome. [source] Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations,HUMAN MUTATION, Issue 7 2009Marc Ferré Abstract We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten primary LHON-causing mtDNA mutations and examining the entire coding sequences of the OPA1 and OPA3 genes, the two genes currently identified in ADOA. Molecular defects were identified in 440 patients (45% of screened patients). Among these, 295 patients (67%) had an OPA1 mutation, 131 patients (30%) had an mtDNA mutation, and 14 patients (3%), belonging to three unrelated families, had an OPA3 mutation. Interestingly, OPA1 mutations were found in 157 (40%) of the 392 apparently sporadic cases of optic atrophy. The eOPA1 locus-specific database now contains a total of 204 OPA1 mutations, including 77 novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1 and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease. © 2009 Wiley-Liss, Inc. [source] CDKN2A mutations in melanoma families from UruguayBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2009A.L. Borges Summary Background, Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35,70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4, and the minor susceptibility gene MC1R. Objectives, To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay. Methods, We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction,single strand conformational polymorphism analysis. The MC1R gene was sequenced. Results, Mutations in CDKN2A were detected in five of six families: c.,34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families. Conclusions, The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range. [source] Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations,HUMAN MUTATION, Issue 7 2009Marc Ferré Abstract We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten primary LHON-causing mtDNA mutations and examining the entire coding sequences of the OPA1 and OPA3 genes, the two genes currently identified in ADOA. Molecular defects were identified in 440 patients (45% of screened patients). Among these, 295 patients (67%) had an OPA1 mutation, 131 patients (30%) had an mtDNA mutation, and 14 patients (3%), belonging to three unrelated families, had an OPA3 mutation. Interestingly, OPA1 mutations were found in 157 (40%) of the 392 apparently sporadic cases of optic atrophy. The eOPA1 locus-specific database now contains a total of 204 OPA1 mutations, including 77 novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1 and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease. © 2009 Wiley-Liss, Inc. [source] Species discovery in marine planktonic invertebrates through global molecular screeningMOLECULAR ECOLOGY, Issue 5 2010ERICA GOETZE Abstract Species discovery through large-scale sampling of mitochondrial diversity, as advocated under DNA barcoding, has been widely criticized. Two of the primary weaknesses of this approach, the use of a single gene marker for species delineation and the possible co-amplification of nuclear pseudogenes, can be circumvented through incorporation of multiple data sources. Here I show that for taxonomic groups with poorly characterized systematics, large-scale genetic screening using a mitochondrial DNA marker can be a very effective approach to species discovery. Global sampling (120 locations) of 1295 individuals of 22 described species of eucalanid copepods identified 15 novel evolutionarily significant units (ESUs) within this marine holoplanktonic family. Species limits were tested under reciprocal monophyly at the mitochondrial (mt) gene 16S rRNA, and 13 of 15 lineages were reciprocally monophyletic under three phylogenetic inference methods. Five of these mitochondrial ESUs also received moderate support for reciprocal monophyly at the independently-inherited nuclear gene, internal transcribed spacer 2 (ITS2). Additional support for the utility of mt DNA as a proxy for species boundaries in this taxon is discussed, including results from related morphological and biogeographic studies. Minimal overlap of intra-ESU and inter-ESU 16S rRNA genetic distances was observed, suggesting that this mt marker performs well for species discovery via molecular screening. Sampling coverage required for the discovery of new ESUs was found to be in the range of >50 individuals/species, well above the sampling intensity of most current DNA Barcoding studies. Large-scale genetic screening can provide critical first data on the presence of cryptic species, and should be used as an approach to generate systematic hypotheses in groups with incomplete taxonomies. [source] Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2008M. R. S. Keshtgar Background: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital. Methods: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash. Results: A total of 18 810 samples were processed, of which 850 (4·5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38·5 per cent (P < 0·001), and MRSA wound isolates fell by 12·7 per cent (P = 0·031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3·78 beds per year (£276 220), compared with the annual mean for the preceding 6 years. The cost of screening was £302 500, making a net loss of £26 280. Compared with 2005, however, there was a net saving of £545 486. Conclusion: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||