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Multiple endocrine neoplasia 2 in Cyprus: evidence for a founder effect.
Fanis, P; Skordis, N; Frangos, S; Christopoulos, G; Spanou-Aristidou, E; Andreou, E; Manoli, P; Mavrommatis, M; Nicolaou, S; Kleanthous, M; Cariolou, M A; Christophidou-Anastasiadou, V; Tanteles, G A; Phylactou, L A; Neocleous, V.
Afiliação
  • Fanis P; Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683, Nicosia, Cyprus.
  • Skordis N; Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683, Nicosia, Cyprus.
  • Frangos S; Division of Pediatric Endocrinology, Paedi Center for Specialized Pediatrics, Nicosia, Cyprus.
  • Christopoulos G; St George's, University of London Medical School at the University of Nicosia, Nicosia, Cyprus.
  • Spanou-Aristidou E; Nuclear Medicine Department, Bank of Cyprus Oncology Center, Nicosia, Cyprus.
  • Andreou E; Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
  • Manoli P; Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683, Nicosia, Cyprus.
  • Mavrommatis M; Dasoupolis Endocrinology Center, Andrea Dimitriou Street Dasoupolis, Nicosia, Cyprus.
  • Nicolaou S; Department of Cardiovascular Genetics and the Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
  • Kleanthous M; Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
  • Cariolou MA; Cyprus School of Molecular Medicine, Nicosia, Cyprus.
  • Christophidou-Anastasiadou V; Division of Pediatric Endocrinology, Makarios III Hospital, Nicosia, Cyprus.
  • Tanteles GA; Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
  • Phylactou LA; Cyprus School of Molecular Medicine, Nicosia, Cyprus.
  • Neocleous V; Department of Cardiovascular Genetics and the Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
J Endocrinol Invest ; 41(10): 1149-1157, 2018 Oct.
Article em En | MEDLINE | ID: mdl-29396759
PURPOSE: Multiple endocrine neoplasia type 2 (MEN2) affects patients with RET proto-oncogene mutations. This cohort study refers to patients who were diagnosed with familial medullary thyroid carcinoma (MTC) and underwent RET genetic testing in Cyprus between years 2002 and 2017. METHODS AND PATIENTS: Forty patients underwent RET testing by Sanger sequencing of exons 10-11 and 13-16. Genotyping with STR genetic markers flanking the RET gene along with Y-chromosome genotyping and haplogroup assignment was also performed. RESULTS: RET mutations were identified in 40 patients from 11 apparently unrelated Cypriot families and two non-familial sporadic cases. Nine probands (69.2%) were heterozygous for p.Cys618Arg, one (7.7%) for p.Cys634Phe, one (7.7%) for the somatic delE632-L633 and two (15.4%) for p.Met918Thr mutations. The mean age at MTC diagnosis of patients carrying p.Cys618Arg was 36.8 ± 14.2 years. The age of pheo diagnosis ranged from 26 to 43 years and appeared simultaneously with MTC in 5/36 (13.9%) cases. The high frequency of the p.Cys618Arg mutation suggested a possible ancestral mutational event. Haplotype analysis was performed in families with and without p.Cys618Arg. Six microsatellite markers covering the RET gene and neighboring regions identified one core haplotype associated with all patients carrying p.Cys618Arg mutation. CONCLUSIONS: The mutation p.Cys618Arg is by far the most prevalent mutation in Cyprus followed by other reported mutations of variable clinical significance. The provided molecular evidence speculates p.Cys618Arg mutation as an ancestral mutation that has spread in Cyprus due to a possible founder effect.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Glândula Tireoide / Carcinoma Medular / Neoplasia Endócrina Múltipla Tipo 2a / Efeito Fundador / Proteínas Proto-Oncogênicas c-ret Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: J Endocrinol Invest Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Chipre

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Glândula Tireoide / Carcinoma Medular / Neoplasia Endócrina Múltipla Tipo 2a / Efeito Fundador / Proteínas Proto-Oncogênicas c-ret Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: J Endocrinol Invest Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Chipre