Dataset Information

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome.

ABSTRACT:

Purpose

Multiple endocrine neoplasia type 1 is a rare tumor syndrome caused by germline mutations of MEN1 gene. Phenotype varies widely, and no definitive correlation with the genotype has been observed. Mutation-negative patients with MEN1-associated tumors represent phenocopies. By comparing mutation-positive and mutation-negative patients, we aimed to identify phenotype features predictive for a positive genetic test and to evaluate the role of MEN1 mutations in phenotype modulation.

Methods

Mutation screeening of MEN1 gene by Sanger sequencing and assessment of clinical data of 189 consecutively enrolled probands and relatives were performed at our national and European Reference Center. Multiple ligation probe amplification analysis of MEN1 gene and Sanger sequencing of CDKN1B were carried out in clinically suspicious but MEN1-negative cases.

Results

Twenty-seven probands and twenty family members carried MEN1 mutations. Five mutations have not been described earlier. Pronouncedly high number of phenocopies (>70%) was observed. Clinical suspicion of MEN1 syndrome emerged at significantly earlier age in MEN1-positive compared to MEN1-negative probands. Gastroenteropancreatic neuroendocrine tumors developed significantly earlier and more frequently in carriers compared to non-carriers. Probands with high-impact (frameshift, nonsense, large deletions) mutations, predicted to affect menin function significantly, developed GEP-NETs more frequently compared to low-impact (inframe and missense) mutation carriers.

Conclusions

MEN1 phenocopy is common and represents a significant confounder for the genetic testing. GEP-NET under 30 years best predicted a MEN1 mutation. The present study thus confirmed a previous proposal and suggested that GEP-NET under 30 years should be considered as a part of the indication criteria for MEN1 mutational analysis.

SUBMITTER: Kovesdi A

PROVIDER: S-EPMC6656790 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome.

Kövesdi Annamária A Tóth Miklós M Butz Henriett H Szücs Nikolette N Sármán Beatrix B Pusztai Péter P Tőke Judit J Reismann Péter P Fáklya Mónika M Tóth Géza G Somogyi Anikó A Borka Katalin K Erdei Annamária A Nagy Endre V EV Deák Veronika V Valkusz Zsuzsanna Z Igaz Péter P Patócs Attila A Grolmusz Vince Kornél VK

Endocrine 20190501 2

<h4>Purpose</h4>Multiple endocrine neoplasia type 1 is a rare tumor syndrome caused by germline mutations of MEN1 gene. Phenotype varies widely, and no definitive correlation with the genotype has been observed. Mutation-negative patients with MEN1-associated tumors represent phenocopies. By comparing mutation-positive and mutation-negative patients, we aimed to identify phenotype features predictive for a positive genetic test and to evaluate the role of MEN1 mutations in phenotype modulation.< ...[more]

PMID: 31044390

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Dataset Information

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome.

Purpose

Methods

Results

Conclusions

Publications

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome.

Similar Datasets

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