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Advisor(s)
Abstract(s)
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.
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Citation
Rodrigues, C; Jorge, Paula; Pires Soares, José; Santos, Isaura; Salomão, Regina; Madeira, Manuela; Vaz-Osório, Rui; Santos, Rosário (2005). Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism. Society of the European Journal of Endocrinology. ISSN 0804-4643, 152:2, p. 193-198
Publisher
Society of the European Journal of Endocrinology