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Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1.
Clin Endocrinol (Oxf). 2009 Jan; 70(1):75-81.CE

Abstract

INTRODUCTION

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene and characterized by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary.

AIM

To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1.

PATIENTS AND METHODS

We studied four unrelated index patients with MEN1, 17 relatives and 100 control subjects. Among the relatives, seven were clinically and/or biochemically affected, while 10 were unaffected. DNA extraction, polymerase chain reaction (PCR) and direct sequencing of the MEN1 exons 2-10 and exon/intron boundaries were performed according to standard procedures.

RESULTS

We identified novel MEN1 gene mutations in three out of four index patients (75%) and in all affected (100%) relatives. Novel mutations included: a frameshift mutation in exon 4 (c.684_685insG) at codon 229 (index patient A); a frameshift mutation in exon 8 (c.1160_1170dupAGGAGCGGCCG) involving codons 387-390 (index patient B); and a missense mutation in exon 4 (c.776T > C), which substitutes leucine with proline at codon 259 (L259P) (index patient C). In the fourth index patient, a common polymorphism (D418D) was detected.

CONCLUSIONS

This is the first report to reveal a high prevalence of novel MEN1 gene mutations among Greek MEN1 patients with apparent absence of genotype-phenotype correlation. Because of the small number of patients examined, the high prevalence detected might be a chance phenomenon.

Authors+Show Affiliations

Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School, Attikon University Hospital, Athens, Greece. molypepa@otenet.grNo 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)

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

Language

eng

PubMed ID

18549467

Citation

Peppa, Melpomeni, et al. "Novel Germline Mutations of the MEN1 Gene in Greek Families With Multiple Endocrine Neoplasia Type 1." Clinical Endocrinology, vol. 70, no. 1, 2009, pp. 75-81.
Peppa M, Boutati E, Kamakari S, et al. Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf). 2009;70(1):75-81.
Peppa, M., Boutati, E., Kamakari, S., Pikounis, V., Peros, G., Koutsodontis, G., Metaxa-Mariatou, V., Economopoulos, T., Raptis, S. A., & Hadjidakis, D. (2009). Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1. Clinical Endocrinology, 70(1), 75-81. https://doi.org/10.1111/j.1365-2265.2008.03308.x
Peppa M, et al. Novel Germline Mutations of the MEN1 Gene in Greek Families With Multiple Endocrine Neoplasia Type 1. Clin Endocrinol (Oxf). 2009;70(1):75-81. PubMed PMID: 18549467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1. AU - Peppa,Melpomeni, AU - Boutati,Eleni, AU - Kamakari,Smaragda, AU - Pikounis,Vasilios, AU - Peros,Georgios, AU - Koutsodontis,Georgios, AU - Metaxa-Mariatou,Vassiliki, AU - Economopoulos,Theofanis, AU - Raptis,Sotirios A, AU - Hadjidakis,Dimitrios, Y1 - 2008/06/12/ PY - 2008/6/14/pubmed PY - 2009/8/4/medline PY - 2008/6/14/entrez SP - 75 EP - 81 JF - Clinical endocrinology JO - Clin Endocrinol (Oxf) VL - 70 IS - 1 N2 - INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene and characterized by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary. AIM: To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1. PATIENTS AND METHODS: We studied four unrelated index patients with MEN1, 17 relatives and 100 control subjects. Among the relatives, seven were clinically and/or biochemically affected, while 10 were unaffected. DNA extraction, polymerase chain reaction (PCR) and direct sequencing of the MEN1 exons 2-10 and exon/intron boundaries were performed according to standard procedures. RESULTS: We identified novel MEN1 gene mutations in three out of four index patients (75%) and in all affected (100%) relatives. Novel mutations included: a frameshift mutation in exon 4 (c.684_685insG) at codon 229 (index patient A); a frameshift mutation in exon 8 (c.1160_1170dupAGGAGCGGCCG) involving codons 387-390 (index patient B); and a missense mutation in exon 4 (c.776T > C), which substitutes leucine with proline at codon 259 (L259P) (index patient C). In the fourth index patient, a common polymorphism (D418D) was detected. CONCLUSIONS: This is the first report to reveal a high prevalence of novel MEN1 gene mutations among Greek MEN1 patients with apparent absence of genotype-phenotype correlation. Because of the small number of patients examined, the high prevalence detected might be a chance phenomenon. SN - 1365-2265 UR - https://www.unboundmedicine.com/medline/citation/18549467/Novel_germline_mutations_of_the_MEN1_gene_in_Greek_families_with_multiple_endocrine_neoplasia_type_1_ L2 - https://doi.org/10.1111/j.1365-2265.2008.03308.x DB - PRIME DP - Unbound Medicine ER -