A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect


Bas V. N. , Aycan Z., Cangul H., Kendall M., Agladioglu S. Y. , Cetinkaya S., ...More

JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, vol.27, pp.383-387, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27
  • Publication Date: 2014
  • Doi Number: 10.1515/jpem-2013-0203
  • Title of Journal : JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
  • Page Numbers: pp.383-387

Abstract

The most common congenital endocrine disorder is congenital hypothyroidism (CH), which can lead to mental retardation if untreated. Majority of the patients have been found to have defects in thyroid development and migration disorders (dysgenesis), and the remaining ones have thyroid hormone synthesis defects (dyshormonogenesis). One of the most common mechanisms to cause dyshormonogenesis is a defect in the thyroid peroxidase (TPO) enzyme. In familial cases, mutations in the TPO gene are fairly prevalent. To date, more than 80 mutations have been identified, which result in variably decreasing TPO bioactivities. Clinical manifestations of TPO defects are typically permanent CH and with or without goiter. In this report, we presented two children with CH who were born to consanguineous parents and were homozygous carriers of a missense (G319R) TPO mutation, the mutation segregated with the disease status in the families confirming its pathogenicity. G319R mutation seemed to be a common cause of CH in Turkish population, which could originate from a common founder ancestor. Moreover, our results also confirmed the phenotypic variability associated with different TPO mutations.