PMID- 9641896
OWN - NLM
STAT- MEDLINE
DCOM- 19980825
LR  - 20191102
IS  - 1435-2443 (Print)
IS  - 1435-2443 (Linking)
VI  - 383
IP  - 2
DP  - 1998 Apr
TI  - Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia 
      type 1.
PG  - 183-6
AB  - 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.
FAU - Karges, W
AU  - Karges W
AD  - Division of Endocrinology, Department of Internal Medicine, University of Ulm, 
      Germany.
FAU - Ludwig, L
AU  - Ludwig L
FAU - Kessler, H
AU  - Kessler H
FAU - Wissmann, A
AU  - Wissmann A
FAU - Wagner, P K
AU  - Wagner PK
FAU - Boehm, B O
AU  - Boehm BO
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Germany
TA  - Langenbecks Arch Surg
JT  - Langenbeck's archives of surgery
JID - 9808285
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Chromosome Aberrations/genetics
MH  - Chromosome Deletion
MH  - Chromosome Disorders
MH  - Chromosomes, Human, Pair 11
MH  - DNA Mutational Analysis
MH  - Female
MH  - Genes, Dominant/genetics
MH  - Genetic Carrier Screening
MH  - Genetic Testing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/diagnosis/*genetics/prevention & control
MH  - Mutation/*genetics
MH  - Neoplasm Proteins/*genetics
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - *Proto-Oncogene Proteins
EDAT- 1998/06/26 00:00
MHDA- 1998/06/26 00:01
CRDT- 1998/06/26 00:00
PHST- 1998/06/26 00:00 [pubmed]
PHST- 1998/06/26 00:01 [medline]
PHST- 1998/06/26 00:00 [entrez]
AID - 10.1007/s004230050115 [doi]
PST - ppublish
SO  - Langenbecks Arch Surg. 1998 Apr;383(2):183-6. doi: 10.1007/s004230050115.