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Predictive genetic screening and clinical findings in multiple endocrine neoplasia type I families

Kopp, I.; Bartsch, D.; Wild, A.; Schilling, T; Nies, C; Bergenfelz, A LU ; Rieder, Harald; Simon, Benjamin and Rothmund, M (2001) In World Journal of Surgery 25(5). p.6-610
Abstract

Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening after genetic counseling. Gene carriers were subjected to extensive clinical screening for MEN-I, including biochemical tests for basal hormone concentrations in blood and urine, a standardized meal stimulation test and imaging procedures (ultrasonography, computed tomography, magnetic resonance imaging). Among index patients of 15 independent... (More)

Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening after genetic counseling. Gene carriers were subjected to extensive clinical screening for MEN-I, including biochemical tests for basal hormone concentrations in blood and urine, a standardized meal stimulation test and imaging procedures (ultrasonography, computed tomography, magnetic resonance imaging). Among index patients of 15 independent MEN-I kindreds, 14 heterozygous MEN1 germline mutations were identified by single-strand conformational variant analysis (SSCV) and direct DNA sequence analysis. Of 51 individuals at risk, 26 predictively tested relatives with the wild-type MEN1 gene could be excluded from further screening procedures because they had not inherited the disease. In all previously presumed unaffected relatives with the mutant gene, our extensive clinical screening program revealed at least one manifestation of MEN-I. Furthermore, 22 additional diagnoses could be established in identified MEN-I patients. We show that mutation analysis enables predictive genetic screening for MEN-I families, providing a valuable tool for genetic counseling and clinical management. An extensive clinical screening program focusing on genetically proven individuals at risk allows detection of MEN-I manifestations at an early, asymptomatic stage of the disease. Controlled, prospective studies are now required to prove whether timely appropriate treatment on the basis of predictive screening might help improve disease-related quality of life and prolong life expectancy in MEN-I kindreds.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
DNA Mutational Analysis, Genetic Testing, Germ-Line Mutation, Humans, Hyperparathyroidism, Multiple Endocrine Neoplasia Type 1, Neoplasm Proteins, Proto-Oncogene Proteins, Journal Article, Research Support, Non-U.S. Gov't
in
World Journal of Surgery
volume
25
issue
5
pages
7 pages
publisher
Springer
external identifiers
  • scopus:0035025614
ISSN
0364-2313
DOI
10.1007/s002680020170
language
English
LU publication?
no
id
0c51ca16-f29b-4f3b-b014-33ebae856753
date added to LUP
2017-05-10 17:34:54
date last changed
2018-05-29 10:48:03
@article{0c51ca16-f29b-4f3b-b014-33ebae856753,
  abstract     = {<p>Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening after genetic counseling. Gene carriers were subjected to extensive clinical screening for MEN-I, including biochemical tests for basal hormone concentrations in blood and urine, a standardized meal stimulation test and imaging procedures (ultrasonography, computed tomography, magnetic resonance imaging). Among index patients of 15 independent MEN-I kindreds, 14 heterozygous MEN1 germline mutations were identified by single-strand conformational variant analysis (SSCV) and direct DNA sequence analysis. Of 51 individuals at risk, 26 predictively tested relatives with the wild-type MEN1 gene could be excluded from further screening procedures because they had not inherited the disease. In all previously presumed unaffected relatives with the mutant gene, our extensive clinical screening program revealed at least one manifestation of MEN-I. Furthermore, 22 additional diagnoses could be established in identified MEN-I patients. We show that mutation analysis enables predictive genetic screening for MEN-I families, providing a valuable tool for genetic counseling and clinical management. An extensive clinical screening program focusing on genetically proven individuals at risk allows detection of MEN-I manifestations at an early, asymptomatic stage of the disease. Controlled, prospective studies are now required to prove whether timely appropriate treatment on the basis of predictive screening might help improve disease-related quality of life and prolong life expectancy in MEN-I kindreds.</p>},
  author       = {Kopp, I. and Bartsch, D. and Wild, A. and Schilling, T and Nies, C and Bergenfelz, A and Rieder, Harald and Simon, Benjamin and Rothmund, M},
  issn         = {0364-2313},
  keyword      = {DNA Mutational Analysis,Genetic Testing,Germ-Line Mutation,Humans,Hyperparathyroidism,Multiple Endocrine Neoplasia Type 1,Neoplasm Proteins,Proto-Oncogene Proteins,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {5},
  pages        = {6--610},
  publisher    = {Springer},
  series       = {World Journal of Surgery},
  title        = {Predictive genetic screening and clinical findings in multiple endocrine neoplasia type I families},
  url          = {http://dx.doi.org/10.1007/s002680020170},
  volume       = {25},
  year         = {2001},
}