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Medizinische Hochschule Hannover 30623 Hannover, Germany
Germ-line mutations in the menin gene cause multiple endocrine neoplasia (MEN1) type 1 (1), but in some kindreds no mutations have yet been identified (2). Tanaka et al. (3) reported menin mutations in nine patients with MEN-1 but none in three kindreds with familial pituitary adenoma.
We examined 26 patients from 9 kindreds with MEN1 (Table 1
)
and a kindred of 19 individuals with 3 cases of isolated Familial
Pituitary Adenoma (Fig. 1)using genomic PCR and direct sequencing as previously described
(4).
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T transversion at the
very 3' end of the splice acceptor site of intron 3. In a patient with
prolactinoma, parathyroid adenoma, and without affected family members,
no mutation could be found in the entire coding sequence of the menin
gene (Table 1
). We also tried to identify menin mutations in a patient
and her aunt, who both presented with hormone-inactive pituitary
adenoma, but no other manifestation of MEN1. The father of the index
patient had a negative magnetic resonance imaging study of the
pituitary, and her uncle had died of growth hormone-producing pituitary
macro-adenoma 5 yr previously and was unavailable for analysis.
Throughout the coding region of the menin gene and adjacent intron
flanks no mutation could be found in either patient. Since the cloning of the menin gene, the clinical diagnosis of MEN1 can be confirmed by menin studies. However, there are no identifiable mutations in the menin coding sequence in approximately 5% of clinically proven MEN1 kindreds, and the rates are seemingly higher in sporadic MEN1 cases (2). It is not clear whether these cases are caused by yet unidentified menin alterations or rather represent a different disease entity. The latter seems to be the case for isolated familial pituitary adenoma, as we could confirm the negative menin results of Tanaka et al. and showed, in addition, that the mode of transmission seemed to be different from the autosomal dominant trait with high penetrance (5) of MEN1.
However, in typical MEN1 with negative studies of the menin coding region, it should be considered that, up to now, three intronic menin
mutations have been found (3, 5 and this study). To account for intronic mutations, intronic exon flanks should be included in the analysis. Studies on genomic DNA could be supplemented by messenger RNA analysis, using the common polymorphisms in the menin coding sequence (1, 2, 5) to ensure the expression of two copies of wild-type menin mRNA.
Footnotes
Received April 22, 1998. Address correspondence to: Bernhard Mayr, M.D., Department of Clinical Endocrinology, Medizinische Hochschule Hannover, 30623 Hannover, Germany.
References
This article has been cited by other articles:
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  K. M A Dreijerink, A. P van Beek, E. G W M Lentjes, J. G Post, R. B van der Luijt, M. R C.-v. Dijk, and C. J M Lips Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease Eur. J. Endocrinol., December 1, 2005; 153(6): 741 - 746. [Abstract] [Full Text] [PDF]
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 S. S. Guo and M. P. Sawicki Molecular and Genetic Mechanisms of Tumorigenesis in Multiple Endocrine Neoplasia Type-1 Mol. Endocrinol., October 1, 2001; 15(10): 1653 - 1664. [Abstract] [Full Text] [PDF]
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), hormone-inactive pituitary adenoma; 
, acromegaly).