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High-resolution melting analysis (HRM) for mutational screening of Dnajc17 gene in patients affected by thyroid dysgenesis

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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.

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Acknowledgements

This work has been partially supported by a grant from the Italian Ministry for University and Research (PRIN 2012 to PEM).

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Author notes

  1. V. Cacace

    Present address: TIGEM, Via Campi Flegrei 34, 80078, Pozzuoli, NA, Italy

Authors and Affiliations

  1. Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli “Federico II”, Via S. Pansini, 5, 80131, Naples, Italy

    I. C. Nettore, S. Desiderio, E. De Nisco, V. Cacace, A. Colao & P. E. Macchia

  2. Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli “Federico II”, Via S. Pansini, 5, 80131, Naples, Italy

    L. Albano, N. Improda & M. Salerno

  3. IEOS, Istituto per l’Endocrinologia e l’Oncologia Sperimentale, “Gaetano Salvatore” Consiglio Nazionale delle Ricerche, Via S. Pansini, 5, 80131, Naples, Italy

    P. Ungaro

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Correspondence to P. E. Macchia.

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Nettore, I.C., Desiderio, S., De Nisco, E. et al. High-resolution melting analysis (HRM) for mutational screening of Dnajc17 gene in patients affected by thyroid dysgenesis. J Endocrinol Invest 41, 711–717 (2018). https://doi.org/10.1007/s40618-017-0795-7

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