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Endocrine Abstracts (2018) 56 P1086 | DOI: 10.1530/endoabs.56.P1086

ECE2018 Poster Presentations: Thyroid Thyroid (non-cancer) (105 abstracts)

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

Dorra Ghorbel 1 , Faten Hadjkacem 1 , Fatma Mnif 1 , Fatma Loukil 1 , Mouna Mnif 1 , Noura Elleuch 2 & Mohamed Abid 1

1Endocrinology-Diabetology Department, CHU Hédi Chaker, Sfax, Tunisia. 2Department of Life Sciences, Faculty of Sciences, Sfax, Tunisia.

We aimed to identify causal mutation(s) in 13 patients with thyroid dyshormonogenesis (TD) from three consanguineous Tunisian families. A 12-year clinical follow-up showed phenotypic variability ranging from the presence to the absence of goiter, sensorineural deafness, and mental retardation. Genetic analysis using microsatellite markers within two candidate genes (TPO and PDS) gave evidence of linkage with the TPO gene. Sequencing of its 17 exons and their flanking intron-exon junctions revealed the previously described c.875C>T (p.S292F) mutation in homozygous state. No additional mutations were found in either a 900 bp of the TPO gene promoter or PDS gene. In silico analysis showed that p.S292F mutation might reduce the catalytic cavity of the TPO which would restrict access of a potential substrate to the catalytic pocket. Using 4SNPs and one microsatellite marker in the TPO gene, an associated haplotype: G-C-G-G-214 was found, giving evidence of a founder mutation.

Conclusion: This is the first description of a TD causing mutation in Tunisia and thus may help to develop a genetic screening protocol for congenital hypothyroidism in the studied region. Although structural modeling suggested a pathogenic effect of this mutation, functional studies are needed. Additional causing and/or modifier genes, together with late diagnosis could explain the clinical variability observed in our patients.

Volume 56

20th European Congress of Endocrinology

Barcelona, Spain
19 May 2018 - 22 May 2018

European Society of Endocrinology 

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