ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P331

Novel MEN1 germline mutations and clinical features in Greek patients with multiple endocrine neoplasia type 1

Melpomeni Peppa1, Vasilios Pikounis1, Smaragda Kamakari2, George Peros3, Theofanis Economopoulos1, Sotirios A Raptis1,4 & Dimitrios Hadjidakis1

1Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Athens University Medical School, Research Institute and Diabetes Center, ‘Attikon’ University Hospital, Athens, Greece; 2BioGenomica, Center for Genetic Research and Analysis, Athens, Greece; 3Fourth Department of Surgery, Athens University Medical School, ‘Attikon’ University Hospital, Athens, Greece; 4Hellenic National Diabetes Center, ‘Attikon’ University Hospital, Athens, Greece.

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder, associated with mutations of the MEN1 gene, characterised 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 4 unrelated index patients (one male and 3 females, age range 30–65 years). Twenty relatives, 8 affected (4 males and 4 females, age range 30–71 years) and 12 unaffected (7 males and 5 females, age range 22–74 years) and 100 control subjects, were also studied. DNA extraction, polymerase chain reaction (PCR) and sequencing the MEN1 exons 2–10 and exon/intron boundaries were performed according to standard procedures.

Results: We identified novel MEN1 gene mutations in 3 out of 4 index patients (75%) and in 8 affected (100%) as well as in 2 unaffected (16.6%) relatives. Novel mutations included a frameshift mutation in exon 4 (c.794-795insG) at codon 229 resulting in the premature termination of menin synthesis at codon 231 (Family 1); a missense mutation in exon 4 (c.886T>C) which substitutes leucine with proline at codon 259 (L259P) (Family 2); a frameshift mutation in exon 8 (c.1270_1280dupAGGAGCGGCCG) involving codons 387–390, resulting in truncation of the menin protein at codon 447 (Family 3). We also found that all our 13 MEN1 carriers (100%) had clinical symptoms and/or biochemical abnormalities. In the fourth index patient, only a common polymorphism (D418D) was detected.

Conclusions: These data indicate the high prevalence of novel MEN1 gene mutations among MEN1 patients and the absence of genotype/phenotype correlation. Mutational analysis for MEN1 identifies healthy carriers who are at a high risk of developing tumours and helps in the clinical management of the patients and their families.

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