I C Nettore1, S Desiderio1, E De Nisco1, V Cacace1,2, L Albano3, N Improda3, P Ungaro4, M Salerno3, A Colao1, P E Macchia5. 1. Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", Via S. Pansini, 5, 80131, Naples, Italy. 2. TIGEM, Via Campi Flegrei 34, 80078, Pozzuoli, NA, Italy. 3. Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Via S. Pansini, 5, 80131, Naples, Italy. 4. IEOS, Istituto per l'Endocrinologia e l'Oncologia Sperimentale, "Gaetano Salvatore" Consiglio Nazionale delle Ricerche, Via S. Pansini, 5, 80131, Naples, Italy. 5. Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", Via S. Pansini, 5, 80131, Naples, Italy. pmacchia@unina.it.
Abstract
BACKGROUND: Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined "thyroid dysgenesis" (TD). TD is generally a sporadic disease but in about 5% of the cases a genetic origin has been demonstrated. Previous studies indicate that Dnajc17 as a candidate modifier gene for hypothyroidism, since it is expressed in the thyroid bud, interacts with NKX2.1 and PAX8 and it has been associated to the hypothyroid phenotype in mice carrying a single Nkx2.1 and Pax8 genes (double heterozygous knock-out). PURPOSE: The work evaluates the possible involvement of DNAJC17 in the pathogenesis of TD. METHODS: High-resolution DNA melting analysis (HRM) and direct sequencing have been used to screen for mutations in the DNAJC17 coding sequence in 89 patients with TD. RESULTS: Two mutations have been identified in the coding sequence of DNAJC17 gene, one in exon 5 (c.350A>C; rs79709714) and one in exon 9 (c.610G>C; rs117485355). The last one is a rare variant, while the rs79709714 is a polymorphism. Both are present in databases and the frequency of the alleles is not different between TD patients and controls. CONCLUSIONS: DNAJC17 mutations are not frequently present in patients with TD.
BACKGROUND:Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined "thyroid dysgenesis" (TD). TD is generally a sporadic disease but in about 5% of the cases a genetic origin has been demonstrated. Previous studies indicate that Dnajc17 as a candidate modifier gene for hypothyroidism, since it is expressed in the thyroid bud, interacts with NKX2.1 and PAX8 and it has been associated to the hypothyroid phenotype in mice carrying a single Nkx2.1 and Pax8 genes (double heterozygous knock-out). PURPOSE: The work evaluates the possible involvement of DNAJC17 in the pathogenesis of TD. METHODS: High-resolution DNA melting analysis (HRM) and direct sequencing have been used to screen for mutations in the DNAJC17 coding sequence in 89 patients with TD. RESULTS: Two mutations have been identified in the coding sequence of DNAJC17 gene, one in exon 5 (c.350A>C; rs79709714) and one in exon 9 (c.610G>C; rs117485355). The last one is a rare variant, while the rs79709714 is a polymorphism. Both are present in databases and the frequency of the alleles is not different between TD patients and controls. CONCLUSIONS:DNAJC17 mutations are not frequently present in patients with TD.
Authors: A M Ferrara; G Rossi; E Zampella; S Di Candia; V Pagliara; I C Nettore; D Capalbo; L De Sanctis; M Baserga; M C Salerno; G Fenzi; P E Macchia Journal: J Endocrinol Invest Date: 2010-11-08 Impact factor: 4.256
Authors: Adeline K Nicholas; Eva G Serra; Hakan Cangul; Saif Alyaarubi; Irfan Ullah; Erik Schoenmakers; Asma Deeb; Abdelhadi M Habeb; Mohammad Almaghamsi; Catherine Peters; Nisha Nathwani; Zehra Aycan; Halil Saglam; Ece Bober; Mehul Dattani; Savitha Shenoy; Philip G Murray; Amir Babiker; Ruben Willemsen; Ajay Thankamony; Greta Lyons; Rachael Irwin; Raja Padidela; Kavitha Tharian; Justin H Davies; Vijith Puthi; Soo-Mi Park; Ahmed F Massoud; John W Gregory; Assunta Albanese; Evelien Pease-Gevers; Howard Martin; Kim Brugger; Eamonn R Maher; V Krishna K Chatterjee; Carl A Anderson; Nadia Schoenmakers Journal: J Clin Endocrinol Metab Date: 2016-08-15 Impact factor: 5.958