Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect

Bougacha-Elleuch, Noura; Charfi, Nadia; Miled, Nabil; Bouhajja, Houda; Belguith, Neila; Mnif, Mouna; Jaurge, Paula; Chikhrouhou, Nessrine; Ayadi, Hammadi; Hachicha, M.; Abid, M.

doi:10.1007/s00431-015-2550-4

Cited by 4 publications

(2 citation statements)

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“…Three different mutations in the TPO gene were identified. The c.1618C>T p.Arg540Ter mutation was reported previously in populations from Japan and the Netherlands [12,15], c.1477G>A p.Gly493Ser was reported in patients from China and Portugal [9,11], and the c.875C>T p.Ser292Phe mutation was reported in patients from Tunis [10]. In family members without TPO mutations, there was no predisposition to developing a goiter.…”

Section: Discussionmentioning

confidence: 55%

“…However, molecular sequencing of the TPO gene has rendered this test irrelevant. Several studies have described the molecular findings of patients with TPO mutations [1,4,[8][9][10][11][12], but only a few them have reported the long-term clinical outcome [13]. Here, we report retrospectively on the long-term follow up (up to 43 years) of 33 patients with TPO mutations and evaluate the effect of TSH serum levels on goiter development.…”

Section: Introductionmentioning

confidence: 98%

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Long-Term Outcome of Patients with TPO Mutations

Tobias

Elias-Assad

Khayat

et al. 2021

JCM

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Introduction: Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect causing congenital hypothyroidism (CH). We aimed to characterize the long-term outcome of patients with TPO deficiency. Methods: Clinical and genetic data were collected retrospectively. Results: Thirty-three patients with primary CH caused by TPO deficiency were enrolled. The follow-up period was up to 43 years. Over time, 20 patients (61%) developed MNG. Eight patients (24%) underwent thyroidectomy: one of them had minimal invasive follicular thyroid carcinoma. No association was found between elevated lifetime TSH levels and the development of goiter over the years. Conclusions: This cohort represents the largest long-term follow up of patients with TPO deficiency. Our results indicate that elevated TSH alone cannot explain the high rate of goiter occurrence in patients with TPO deficiency, suggesting additional factors in goiter development. The high rate of MNG development and the risk for thyroid carcinoma indicate a need for long-term follow up with annual ultrasound scans.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 98%

Long-Term Outcome of Patients with TPO Mutations

Tobias

Elias-Assad

Khayat

et al. 2021

JCM

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Curating the gnomAD database: Report of novel variants in the thyroid peroxidase gene using in silico bioinformatics algorithms and a literature review

Molina

Pio

Scheps

et al. 2022

Molecular and Cellular Endocrinology

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Congenital hypothyroidism and thyroid cancer

Penna

Rubio

Brust

et al. 2021

Endocrine-Related Cancer

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Differentiated thyroid carcinoma (DTC) combined whit congenital hypothyroidism (CH) is a rare situation, and there is no well-established causal relationship. CH is a common congenital endocrine, while DTC occurring in childhood represents 0.4% to 3% of all malignancies at this stage of life. The association of CH with DTC could be related to dyshormonogenetic goiter (DHG) or developmental abnormalities. This review will explore the clinical features and the molecular mechanisms potentially associated with the appearance of DTC in CH: sporadic somatic driver mutations, chronic increase of thyroid-stimulating hormone (TSH) levels, higher concentrations hydrogen peroxide (H2O2), Borelain /CDCA8 gene mutations and in others genes associated with CH - either alone or associated with the mechanisms involved in dyshormonogenesis. There are some pitfalls in the diagnosis of thyroid cancer in patients with CH with nodular goiter, as the proper cytological diagnosis of nodules of patients with dyshormonogenesis might be demanding due to the specific architectural and cytological appearance, which may lead to an erroneous interpretation of malignancy. The purpose of this article is to suggest an analytical framework that embraces the fundamental relationships between the various aspects of CH and CDT. In face of this scenario, the entire genetic and epigenetic context, the complex functioning and cross talk of cell signaling may determine cellular mechanisms promoting both the maintenance of the differentiated state of the thyroid follicular cell and the disruption of its homeostasis leading to cancer. Whereas, the exact mechanisms for thyroid cancer development in CH remain to be elucidated.

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Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect

Cited by 4 publications

References 47 publications

Long-Term Outcome of Patients with TPO Mutations

Long-Term Outcome of Patients with TPO Mutations

Curating the gnomAD database: Report of novel variants in the thyroid peroxidase gene using in silico bioinformatics algorithms and a literature review

Congenital hypothyroidism and thyroid cancer

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