scholarly journals Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect

2003 ◽  
Vol 22 (3) ◽  
pp. 259-259 ◽  
Author(s):  
Carina M. Rivolta ◽  
Sebastián A. Esperante ◽  
Laura Gruñeiro-Papendieck ◽  
Ana Chiesa ◽  
Christian M. Moya ◽  
...  
Keyword(s):  
Thyroid Peroxidase ◽  
Peroxidase Gene ◽  
Congenital Goiter ◽  
Iodide Organification Defect ◽  
Organification Defect ◽  
Inactivating Mutations

Partial iodide organification defect caused by a novel mutation of the thyroid peroxidase gene in three siblings

2003 ◽  
Vol 59 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Tomio Kotani ◽  
Kazumi Umeki ◽  
Jun-ichi Kawano ◽  
Tatsuo Suganuma ◽  
Akira Hishinuma ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Thyroid Peroxidase ◽  
Peroxidase Gene ◽  
Iodide Organification Defect ◽  
Organification Defect

scholarly journals Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism

2005 ◽  
Vol 152 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Carina Rodrigues ◽  
Paula Jorge ◽  
José Pires Soares ◽  
Isaura Santos ◽  
Regina Salomão ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Mutation Screening ◽  
Gene Mutations ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Molecular Testing ◽  
Missense Mutations ◽  
Human Thyroid Peroxidase ◽  
Iodide Organification Defect ◽  
Organification Defect

Objective: Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme. Subjects and methods: The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1–17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns. Results: Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected. Conclusion: The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.

scholarly journals CNS Hypomyelination in Rat Terrier Dogs with Congenital Goiter and a Mutation in the Thyroid Peroxidase Gene

2007 ◽  
Vol 44 (1) ◽  
pp. 50-56 ◽  
Author(s):  
R. Pettigrew ◽  
J. C. Fyee ◽  
B. L. Gregory ◽  
D. Lipsitz ◽  
A. DeLahunta ◽  
...  
Keyword(s):  
Thyroid Peroxidase ◽  
Peroxidase Gene ◽  
Congenital Goiter

Abnormal Thyroid Peroxidase Causing Iodide Organification Defect

1972 ◽  
Vol 34 (4) ◽  
pp. 607-616 ◽  
Author(s):  
HUGO NIEPOMNISZCZE ◽  
LESLIE J. DEGROOT ◽  
GARRETT A. HAGEN
Keyword(s):  
Thyroid Peroxidase ◽  
Iodide Organification Defect ◽  
Organification Defect

scholarly journals Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism

2002 ◽  
pp. 491-498 ◽  
Author(s):  
K Umeki ◽  
T Kotani ◽  
J Kawano ◽  
T Suganuma ◽  
I Yamamoto ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Congenital Hypothyroidism ◽  
Cellular Localization ◽  
Thyroid Peroxidase ◽  
Missense Mutations ◽  
Thyroid Hormone Biosynthesis ◽  
Thyroid Dyshormonogenesis ◽  
Hormone Biosynthesis ◽  
Iodide Organification Defect ◽  
Organification Defect

OBJECTIVE: Thyroid peroxidase (TPO) deficiency is one of the causes of thyroid dyshormonogenesis, because TPO plays a key role in thyroid hormone biosynthesis. To determine the frequency and pattern of TPO abnormalities, we have been screening TPO genes of patients with congenital goitrous hypothyroidism. SUBJECTS AND METHODS: TPO genes of a patient with congenital goitrous hypothyroidism and her parents were directly sequenced, and two novel missense mutations (R665W and G771R) were found. The former was derived from her father and the latter from her mother. R665 and G771 were well conserved in the peroxidase superfamily. When mRNAs containing each of the mutations were transfected into CHO-K1 cells, each cell showed faint TPO enzyme activity. However, immunofluorescence and immunoelectron microscopic analyses revealed that neither of the mutated TPOs reached the plasma membrane. CONCLUSIONS: Two novel missense mutations in the TPO gene were found. TPO proteins encoded by these mutated alleles showed abnormal cellular localization; namely, localization on the plasma membrane was disturbed. The loss of plasma membrane localization in mutated TPOs brought about the iodide organification defect, which was diagnosed as congenital hypothyroidism.

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