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19 results on '"Mautner, V.F."'

7. Double NF1 inactivation affects adrenocortical function in NF1Prx1 mice and a human patient

Author

Kobus, K., Hartl, D., Ott, C.E., Osswald, M., Huebner, A., Hagen, M. von der, Emmerich, D., Kuhnisch, J., Morreau, H., Hes, F.J., Mautner, V.F., Harder, A., Tinschert, S., Mundlos, S., Kolanczyk, M., and Clinical sciences

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Neurofibromatosis 1, Adolescent, Adrenal Cortex/metabolism, Science, Loss of Heterozygosity, Neurofibromatosis 1/genetics, Adrenal Hyperplasia, Congenital/genetics, Mice, Adrenocorticotropic Hormone, Adrenocorticotropic Hormone/metabolism, Animals, Humans, Child, Medicine(all), Homeodomain Proteins, Neurofibromin 1, Adrenal Hyperplasia, Congenital, nervous system diseases, Child, Preschool, Adrenal Cortex, Medicine, Female, Homeodomain Proteins/genetics, Neurofibromin 1/genetics, Research Article
Abstract

BackgroundNeurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5-5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis.Materials and methodsWe analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient.ResultsIn Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female specific increase of cAMP concentration in murine adrenal lysates. Complementarily, we characterized a patient with neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH-independent cortisol overproduction. Comparison of normal control tissue- and adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred in the hyperplastic adrenal gland.ConclusionsOur data suggest that biallelic loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is involved in the regulation of adrenal cortex function in mice and humans.

Published
2014

18. The diagnosis and management of neurofibromatosis 2 in childhood

Author

MacCollin, M. and Mautner, V.F.

Abstract

Neurofibromatosis 2 (NF2) is an autosomal-dominant condition that causes multiple benign nervous system tumors, especially vestibular schwannoma. Although frequently confused with the more common neurofibromatosis 1, NF2 presents a distinct set of diagnostic, genetic, and management issues. The presentation and natural history of NF2 differs in children and adults, with eighth nerve dysfunction often overshadowed by the effects of other tumors on the nervous system. Molecular diagnostics is an important tool for early recognition of NF2, and when performed in the context of appropriate counseling and follow-up, may lead to a better final outcome of the disease. Further research into the molecular genetic etiology of NF2 promises to broaden the possibilities of therapy for this devastating disorder.

Published
1998
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