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Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1.
Clin Endocrinol (Oxf). 2007 Sep; 67(3):377-84.CE

Abstract

OBJECTIVE

To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1). Settings Non-profit academic centre.

PATIENTS

Fourteen Brazilian families with MEN1 and 141 at-risk relatives.

RESULTS

We identified 12 different MEN1 disease-causing mutations, seven of them previously unreported: 308delC; 375del21; 549A>T (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by mitochondrial-DNA and Y-chromosome haplotype analyses. Most of the MEN1 single point mutations involved evolutionarily conserved residues, whereas most of the deletion/frameshift changes occurred in GC-rich repetitive regions. Genetic screening of 141 at-risk family members identified 38 MEN1 mutation carriers, 37 (97.4%) of whom had at least one major MEN1-related tumour upon clinical investigation.

CONCLUSIONS

High frequencies of MEN1 gene mutations were detected in Brazilian families with MEN1, including seven new genetic mutations that are predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data underscore the need to implement a systematic MEN1 screening programme in Brazil.

Authors+Show Affiliations

Unidade de Endocrinologia Genética LIM-25, Endocrinologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17555499

Citation

Toledo, Rodrigo A., et al. "Novel MEN1 Germline Mutations in Brazilian Families With Multiple Endocrine Neoplasia Type 1." Clinical Endocrinology, vol. 67, no. 3, 2007, pp. 377-84.
Toledo RA, Lourenço DM, Coutinho FL, et al. Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf). 2007;67(3):377-84.
Toledo, R. A., Lourenço, D. M., Coutinho, F. L., Quedas, E., Mackowiack, I., Machado, M. C., Montenegro, F., Cunha-Neto, M. B., Liberman, B., Pereira, M. A., Correa, P. H., & Toledo, S. P. (2007). Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1. Clinical Endocrinology, 67(3), 377-84.
Toledo RA, et al. Novel MEN1 Germline Mutations in Brazilian Families With Multiple Endocrine Neoplasia Type 1. Clin Endocrinol (Oxf). 2007;67(3):377-84. PubMed PMID: 17555499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1. AU - Toledo,Rodrigo A, AU - Lourenço,Delmar M,Jr AU - Coutinho,Flavia L, AU - Quedas,Elisangela, AU - Mackowiack,Ivone, AU - Machado,Marcel C C, AU - Montenegro,Fabio, AU - Cunha-Neto,Malebranche B C, AU - Liberman,Bernardo, AU - Pereira,Maria A A, AU - Correa,Pedro H S, AU - Toledo,Sergio P A, Y1 - 2007/06/06/ PY - 2007/6/9/pubmed PY - 2011/10/28/medline PY - 2007/6/9/entrez SP - 377 EP - 84 JF - Clinical endocrinology JO - Clin Endocrinol (Oxf) VL - 67 IS - 3 N2 - OBJECTIVE: To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1). Settings Non-profit academic centre. PATIENTS: Fourteen Brazilian families with MEN1 and 141 at-risk relatives. RESULTS: We identified 12 different MEN1 disease-causing mutations, seven of them previously unreported: 308delC; 375del21; 549A>T (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by mitochondrial-DNA and Y-chromosome haplotype analyses. Most of the MEN1 single point mutations involved evolutionarily conserved residues, whereas most of the deletion/frameshift changes occurred in GC-rich repetitive regions. Genetic screening of 141 at-risk family members identified 38 MEN1 mutation carriers, 37 (97.4%) of whom had at least one major MEN1-related tumour upon clinical investigation. CONCLUSIONS: High frequencies of MEN1 gene mutations were detected in Brazilian families with MEN1, including seven new genetic mutations that are predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data underscore the need to implement a systematic MEN1 screening programme in Brazil. SN - 0300-0664 UR - https://www.unboundmedicine.com/medline/citation/17555499/Novel_MEN1_germline_mutations_in_Brazilian_families_with_multiple_endocrine_neoplasia_type_1_ L2 - https://doi.org/10.1111/j.1365-2265.2007.02895.x DB - PRIME DP - Unbound Medicine ER -