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Constantine A Stratakis - One of the best experts on this subject based on the ideXlab platform.
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men1 men4 and carney complex pathology and Molecular Genetics
Neuroendocrinology, 2016Co-Authors: Marie Helene Schernthanerreiter, Giampaolo Trivellin, Constantine A StratakisAbstract:Pituitary adenomas are a common feature of a subset of endocrine neoplasia syndromes, which have otherwise highly variable disease manifestations. We provide here a review of the clinical features and human Molecular Genetics of multiple endocrine neoplasia (MEN) type 1 and 4 (MEN1 and MEN4, respectively) and Carney complex (CNC). MEN1, MEN4, and CNC are hereditary autosomal dominant syndromes that can present with pituitary adenomas. MEN1 is caused by inactivating mutations in the MEN1 gene, whose product menin is involved in multiple intracellular pathways contributing to transcriptional control and cell proliferation. MEN1 clinical features include primary hyperparathyroidism, pancreatic neuroendocrine tumours and prolactinomas as well as other pituitary adenomas. A subset of patients with pituitary adenomas and other MEN1 features have mutations in the CDKN1B gene; their disease has been called MEN4. Inactivating mutations in the type 1α regulatory subunit of protein kinase A (PKA; the PRKAR1A gene), that lead to dysregulation and activation of the PKA pathway, are the main genetic cause of CNC, which is clinically characterised by primary pigmented nodular adrenocortical disease, spotty skin pigmentation (lentigines), cardiac and other myxomas and acromegaly due to somatotropinomas or somatotrope hyperplasia.
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carney complex and mccune albright syndrome an overview of clinical manifestations and human Molecular Genetics
Molecular and Cellular Endocrinology, 2014Co-Authors: Paraskevi Salpea, Constantine A StratakisAbstract:Endocrine neoplasia syndromes feature a wide spectrum of benign and malignant tumors of endocrine and non-endocrine organs associated with other clinical manifestations. This study outlines the main clinical features, genetic basis, and Molecular mechanisms behind two multiple endocrine neoplasia syndromes that share quite a bit of similarities, but one can be inherited whereas the other is always sporadic, Carney complex (CNC) and McCune-Albright (MAS), respectively. Spotty skin pigmentation, cardiac and other myxomas, and different types of endocrine tumors and other characterize Carney complex, which is caused largely by inactivating Protein kinase A, regulatory subunit, type I, Alpha (PRKAR1A) gene mutations. The main features of McCune-Albright are fibrous dysplasia of bone (FD), cafe-au-lait macules and precocious puberty; the disease is caused by activating mutations in the Guanine Nucleotide-binding protein, Alpha-stimulating activity polypeptide (GNAS) gene which are always somatic. We review the clinical manifestations of the two syndromes and provide an update on their Molecular Genetics.
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clinical and Molecular Genetics of acromegaly men1 carney complex mccune albright syndrome familial acromegaly and genetic defects in sporadic tumors
Reviews in Endocrine & Metabolic Disorders, 2008Co-Authors: Anelia Horvath, Constantine A StratakisAbstract:Pituitary tumors are among the most common neoplasms in man; they account for approximately 15% of all primary intracranial lesions (Jagannathan et al., Neurosurg Focus, 19:E4, 2005). Although almost never malignant and rarely clinically expressed, pituitary tumors may cause significant morbidity in affected patients. First, given the critical location of the gland, large tumors may lead to mass effects, and, second, proliferation of hormone-secreting pituitary cells leads to endocrine syndromes. Acromegaly results from oversecretion of growth hormone (GH) by the proliferating somatotrophs. Despite the significant efforts made over the last decade, still little is known about the genetic causes of common pituitary tumors and even less is applied from this knowledge therapeutically. In this review, we present an update on the genetic syndromes associated with pituitary adenomas and discuss the related genetic defects. We next review findings on sporadic, non-genetic, pituitary tumors with an emphasis on pathways and animal models of pituitary disease. In conclusion, we attempt to present an overall, integrative approach to the human Molecular Genetics of both familiar and sporadic pituitary tumors.
Friedrich C Luft - One of the best experts on this subject based on the ideXlab platform.
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Molecular Genetics of salt sensitivity and hypertension
Drug Metabolism and Disposition, 2001Co-Authors: Friedrich C LuftAbstract:For the past decade, hypertension research has shifted strongly in the direction of Molecular Genetics. The success stories are the monogenic hypertensive syndromes. Classic linkage analyses have located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. Furthermore, a recent gain-of-function mutation has recently been described in the gene for the mineralocorticoid receptor. These genes have been cloned and their functions elucidated. Other monogenic syndromes are currently being intensively studied. However, in the area of primary hypertension, the successes have relied on the candidate gene approach. Allelic variants in the genes for angiotensinogen, α-adducin, the β2-adrenergic receptor, the G-protein β3-subunit, and the T594M mutation in the β-subunit of the epithelial sodium channel have been identified; however, the importance of these allelic variants to primary hypertension as a whole is not yet clear. Recently, an association approach was employed to implicate the mineralocorticoid receptor gene in salt-sensitivity. Linkage approaches have been attempted and the β-subunit of the epithelial sodium channel has been linked to hypertension and to blood pressure as a quantitative trait locus. New approaches are necessary to elucidate salt-sensitive hypertension. The analysis of multiple genes simultaneously in terms of a metabolic control analysis may provide a more promising approach.
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Molecular Genetics of human hypertension
Current Opinion in Nephrology and Hypertension, 2000Co-Authors: Friedrich C LuftAbstract:The year 1999 saw considerable activity in the area of hypertension-related Molecular Genetics. Several new monogenic hypertensive disorders, as well as a monogenic form of hypotension, were elucidated. Molecular Genetics has made significant inroads in explaining basic mechanisms of magnesium homeo
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Molecular Genetics of human hypertension
Journal of Hypertension, 1998Co-Authors: Friedrich C LuftAbstract:For the past decade, hypertension research has shifted strongly in the direction of Molecular Genetics. The success stories are the monogenic hypertensive syndromes. Classic linkage analyses has located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. The genes have been cloned and their function elucidated. Other monogenic syndromes are currently being intensively studied. However, in the area of primary hypertension, the successes have relied on the candidate gene approach. Allelic variants in the genes for angiotensinogen, α-adducin, β 2 -adrenergic receptor, the G-protein β 3 -subunit and the T594M mutation in the β-subunit of the epithelial sodium channel have been identified; however, the importance of these allelic variants to primary hypertension as a whole, is not yet clear. A variant in the angiotensin-converting enzyme gene could not, initially, be convincingly associated with hypertension, but more recent analyses suggest an influence of the deletion allele on blood pressure in men, but apparently not in women. In all likelihood we are dealing with many genes with small effects. Affected sibling pair linkage analyses will probably not be successful in identifying the loci of these genes. To find new genes, novel approaches will be necessary, including searching for quantitative trait loci linked to blood pressure in normotensive persons, haplotype sharing methodology in trios and family units, the use of better study designs, and the investigation of isolated populations. Finally, rethinking the phenotype 'hypertension' and its intermediates must also receive priority.
Michael P Lesser - One of the best experts on this subject based on the ideXlab platform.
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solving cryptogenic histories using host and parasite Molecular Genetics the resolution of littorina littorea s north american origin
Molecular Ecology, 2008Co-Authors: April M H Blakeslee, James E Byers, Michael P LesserAbstract:Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail's ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used Molecular Genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of approxiamtely 500 years ago from Europe for both host and parasite--thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
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solving cryptogenic histories using host and parasite Molecular Genetics the resolution of littorina littorea s north american origin
Molecular Ecology, 2008Co-Authors: April M H Blakeslee, James E Byers, Michael P LesserAbstract:Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail’s ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used Molecular Genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of ~500 years ago from Europe for both host and parasite — thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
April M H Blakeslee - One of the best experts on this subject based on the ideXlab platform.
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solving cryptogenic histories using host and parasite Molecular Genetics the resolution of littorina littorea s north american origin
Molecular Ecology, 2008Co-Authors: April M H Blakeslee, James E Byers, Michael P LesserAbstract:Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail's ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used Molecular Genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of approxiamtely 500 years ago from Europe for both host and parasite--thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
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solving cryptogenic histories using host and parasite Molecular Genetics the resolution of littorina littorea s north american origin
Molecular Ecology, 2008Co-Authors: April M H Blakeslee, James E Byers, Michael P LesserAbstract:Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail’s ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used Molecular Genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of ~500 years ago from Europe for both host and parasite — thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
James E Byers - One of the best experts on this subject based on the ideXlab platform.
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solving cryptogenic histories using host and parasite Molecular Genetics the resolution of littorina littorea s north american origin
Molecular Ecology, 2008Co-Authors: April M H Blakeslee, James E Byers, Michael P LesserAbstract:Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail's ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used Molecular Genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of approxiamtely 500 years ago from Europe for both host and parasite--thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
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solving cryptogenic histories using host and parasite Molecular Genetics the resolution of littorina littorea s north american origin
Molecular Ecology, 2008Co-Authors: April M H Blakeslee, James E Byers, Michael P LesserAbstract:Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail’s ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used Molecular Genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of ~500 years ago from Europe for both host and parasite — thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
