TY - JOUR
T1 - A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
AU - Baş, Veysel Nijat
AU - Aycan, Zehra
AU - Cangul, Hakan
AU - Kendall, Michaela
AU - Aǧladioǧlu, Sebahat Yilmaz
AU - Çetinkaya, Semra
AU - Maher, Eamonn R.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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.
AB - 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.
KW - congenital hypothyroidism
KW - founder effect
KW - mutation
KW - thyroid peroxidase gene
UR - http://www.scopus.com/inward/record.url?scp=84896763755&partnerID=8YFLogxK
UR - https://www.degruyter.com/document/doi/10.1515/jpem-2013-0203/html
U2 - 10.1515/jpem-2013-0203
DO - 10.1515/jpem-2013-0203
M3 - Article
C2 - 24158420
AN - SCOPUS:84896763755
SN - 0334-018X
VL - 27
SP - 383
EP - 387
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 3-4
ER -