Multiple endocrine neoplasia syndrome type 1 (MEN-1) in Sardinian population: low prevalence of Men-1 mutations and detection of a new inactivating mutation of the CDKI gene p27

M. Mastinu; F. Cetani; C. Marcocci; E. Pardi; A. Cappai; C. Satta; F. Badessi; A. Delitala; R. Lai; G. Fanciulli; S. Mariotti

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Endocrine Abstracts (2012) 29 P839

ICEECE2012 Poster Presentations Endocrine tumours and neoplasia (112 abstracts)

Multiple endocrine neoplasia syndrome type 1 (MEN-1) in Sardinian population: low prevalence of Men-1 mutations and detection of a new inactivating mutation of the CDKI gene p27

M. Mastinu ¹ , F. Cetani ² , C. Marcocci ² , E. Pardi ² , A. Cappai ¹ , C. Satta ¹ , F. Badessi ³ , A. Delitala ³ , R. Lai ³ , G. Fanciulli ³ & S. Mariotti ¹

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University of Sassari, Sassari, Italy.

Introduction: The genetic basis of multiple endocrine neoplasia type 1 (MEN-1) syndrome is often represented by inactivating mutations of Men-1 gene, found in 50–80% of different series. Recently, other mutations of genes encoding for the CDKI complex (p15, p18, p21, and p27) and of the AIP gene have been described in a small number of Men-1-negative patients.

Methods and results: Since 2002 we tested for Men-1 mutations 16 patients born and living in Sardinia, an island with approximately 1,500,000 inhabitants and peculiar genetic background due to long-lasting isolation. The series included 13 patients with a clear MEN-1 phenotype (7 with familial history, for a total of 5 families, and 6 apparently sporadic) and 3 with apparent MEN-1 phenotype (1 familial and 2 apparently sporadic). Men-1 mutations were detected in only 3 cases (2 familial, 1 sporadic), corresponding to 27.2% of patients with clear MEN-1 phenotype. Identified mutations were Arg229His in exon 4 and splicing 894-9 G>A (familial cases) and frameshift 1284-of G in the exon 8 (sporadic case). We then started to look for the presence of other mutations in Men-1-negative patients and to date we completed the analysis for p27. A new p27 mutation (c.372_373delCT in exon 1) was found in a patient with an apparently sporadic typical MEN-1 syndrome (neuroendocrine tumors of the pancreas and distal duodenum and primary hyperparathyroidism due to multiple parathyroid adenomas).

Conclusion: These results suggest that in the particular context of the Sardinian population, the genetic basis of MEN-1 could be different from that commonly observed, with a relatively low prevalence of Men-1 as compared to non-Men-1 mutations. The detection in this small series of a new p27 mutation confirms that a complete screening for rare mutations is advisable in all Men-1 negative patients with clear MEN-1 phenotype, irrespective of positive family history.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.