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Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia type 1.
Langenbecks Arch Surg. 1998 Apr; 383(2):183-6.LA

Abstract

INTRODUCTION

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the development of multiple endocrine adenomas, typically in the pancreas, anterior pituitary, and parathyroid glands. The disease is associated with germ-line mutations of the menin gene, a putative tumor-suppressor gene located on human chromosome 11q13.

METHODS

To facilitate the diagnosis and prediction of MEN1 in patients and their relatives, we developed a molecular two-step strategy to screen for menin gene mutations. DNA fragments covering the entire menin coding sequence are generated from patient cDNA by polymerase reaction (PCR) and subsequently analyzed by single-strand conformational polymorphism electrophoresis (SSCP). Fragments with aberrant SSCP migration are DNA-sequenced to directly characterize menin mutations. In a second diagnostic step, genomic DNA of healthy relatives of the corresponding MEN1 index patient is analyzed by PCR, with only the specific exon amplified harboring the family-specific mutation. Mutation-specific restriction enzyme digestion of this PCR product finally allows the identification of mutation carriers through pathological restriction fragment patterns.

RESULTS

Using this approach, we identified an in-frame deletion mutation (delta Tyr Met) located in menin exon 4 (codon 227-228) that co-segregates with the disease phenotype in a large MEN1 family from Southern Germany.

CONCLUSION

It is likely that the direct molecular analysis of menin gene mutations will replace the genetic and biochemical screening tests currently used in the clinical management of MEN1 families. In addition, these studies may provide clues to the tumor biology of both sporadic and MEN1-associated endocrine adenomas.

Authors+Show Affiliations

Division of Endocrinology, Department of Internal Medicine, University of Ulm, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

9641896

Citation

Karges, W, et al. "Menin Mutations in the Diagnosis and Prediction of Multiple Endocrine Neoplasia Type 1." Langenbeck's Archives of Surgery, vol. 383, no. 2, 1998, pp. 183-6.
Karges W, Ludwig L, Kessler H, et al. Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia type 1. Langenbecks Arch Surg. 1998;383(2):183-6.
Karges, W., Ludwig, L., Kessler, H., Wissmann, A., Wagner, P. K., & Boehm, B. O. (1998). Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia type 1. Langenbeck's Archives of Surgery, 383(2), 183-6.
Karges W, et al. Menin Mutations in the Diagnosis and Prediction of Multiple Endocrine Neoplasia Type 1. Langenbecks Arch Surg. 1998;383(2):183-6. PubMed PMID: 9641896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia type 1. AU - Karges,W, AU - Ludwig,L, AU - Kessler,H, AU - Wissmann,A, AU - Wagner,P K, AU - Boehm,B O, PY - 1998/6/26/pubmed PY - 1998/6/26/medline PY - 1998/6/26/entrez SP - 183 EP - 6 JF - Langenbeck's archives of surgery JO - Langenbecks Arch Surg VL - 383 IS - 2 N2 - INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the development of multiple endocrine adenomas, typically in the pancreas, anterior pituitary, and parathyroid glands. The disease is associated with germ-line mutations of the menin gene, a putative tumor-suppressor gene located on human chromosome 11q13. METHODS: To facilitate the diagnosis and prediction of MEN1 in patients and their relatives, we developed a molecular two-step strategy to screen for menin gene mutations. DNA fragments covering the entire menin coding sequence are generated from patient cDNA by polymerase reaction (PCR) and subsequently analyzed by single-strand conformational polymorphism electrophoresis (SSCP). Fragments with aberrant SSCP migration are DNA-sequenced to directly characterize menin mutations. In a second diagnostic step, genomic DNA of healthy relatives of the corresponding MEN1 index patient is analyzed by PCR, with only the specific exon amplified harboring the family-specific mutation. Mutation-specific restriction enzyme digestion of this PCR product finally allows the identification of mutation carriers through pathological restriction fragment patterns. RESULTS: Using this approach, we identified an in-frame deletion mutation (delta Tyr Met) located in menin exon 4 (codon 227-228) that co-segregates with the disease phenotype in a large MEN1 family from Southern Germany. CONCLUSION: It is likely that the direct molecular analysis of menin gene mutations will replace the genetic and biochemical screening tests currently used in the clinical management of MEN1 families. In addition, these studies may provide clues to the tumor biology of both sporadic and MEN1-associated endocrine adenomas. SN - 1435-2443 UR - https://www.unboundmedicine.com/medline/citation/9641896/Menin_mutations_in_the_diagnosis_and_prediction_of_multiple_endocrine_neoplasia_type_1_ L2 - https://dx.doi.org/10.1007/s004230050115 DB - PRIME DP - Unbound Medicine ER -