Abstract
To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon-intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband's germlinemutationswere found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both themutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 481-485 |
| Number of pages | 5 |
| Journal | Endocrine |
| Volume | 40 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Dec 2011 |
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Keywords
- Medullary thyroid cancer
- MEN1
- MEN2
- Primary hyperparathyroidism
ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family. / Mastroianno, Sandra; Torlontano, Massimo; Scillitani, Alfredo; D'Aloiso, Leonardo; Verrienti, Antonella; Bonfitto, Nazario; De Bonis, Antonio; D'Agruma, Leonardo; Muscarella, Lucia Anna; Guarnieri, Vito; Dicembrino, Franca; Maranghi, Marianna; Durante, Cosimo; Filetti, Sebastiano.
In: Endocrine, Vol. 40, No. 3, 12.2011, p. 481-485.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family
AU - Mastroianno, Sandra
AU - Torlontano, Massimo
AU - Scillitani, Alfredo
AU - D'Aloiso, Leonardo
AU - Verrienti, Antonella
AU - Bonfitto, Nazario
AU - De Bonis, Antonio
AU - D'Agruma, Leonardo
AU - Muscarella, Lucia Anna
AU - Guarnieri, Vito
AU - Dicembrino, Franca
AU - Maranghi, Marianna
AU - Durante, Cosimo
AU - Filetti, Sebastiano
PY - 2011/12
Y1 - 2011/12
N2 - To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon-intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband's germlinemutationswere found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both themutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases.
AB - To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon-intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband's germlinemutationswere found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both themutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases.
KW - Medullary thyroid cancer
KW - MEN1
KW - MEN2
KW - Primary hyperparathyroidism
UR - http://www.scopus.com/inward/record.url?scp=84858758372&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858758372&partnerID=8YFLogxK
U2 - 10.1007/s12020-011-9501-2
DO - 10.1007/s12020-011-9501-2
M3 - Article
C2 - 21678021
AN - SCOPUS:84858758372
VL - 40
SP - 481
EP - 485
JO - Endocrine
JF - Endocrine
SN - 1355-008X
IS - 3
ER -