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Disease Markers
Volume 29, Issue 2, Pages 63-69
http://dx.doi.org/10.3233/DMA-2010-0727

SLC26A4 Variations Among Graves’ Hyper-Functioning Thyroid Gland

Hassen Hadj-Kacem,1 Rihab Kallel,1 Salima Belguith-Maalej,1 Mouna Mnif,2 Ilhem Charfeddine,3 Abdelmounem Ghorbel,3 Mohamed Abid,2 Hammadi Ayadi,1 and Saber Masmoudi1

1Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax, Tunisia
2Service d'Endocrinology, CHU Hédi Chaker, Sfax, Tunisia
3Service d'ORL, CHU Habib Bourguiba, Sfax, Tunisia

Received 21 October 2010; Accepted 21 October 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Deleterious mutations of SLC26A4 cause Pendred syndrome (PS), an autosomal recessive disorder comprising goitre and deafness with enlarged vestibular aqueducts (EVA), and nonsyndromic hearing loss (NSHL). However, the SLC26A4 hyperactivity was recently associated with the emergence of autoimmune thyroid diseases (AITD) and asthma among human and mouse model. Here, by direct sequencing, we investigate the sequences of the 20 coding exons (2 to 21) of SLC26A4 and their flanking intron-exon junctions among patients affected with Graves' disease (GD) hyperthyroidism. Ten mono-allelic variants were identified, seven of which are intronic and previously unreported. Two, c.898A>C (p.I300L) and c.1061T>C (p.F354S), of the three exonic variants are non synonymous. The p.F354S variant is already described to be involved in PS or NSHL inheritances. The exploration by PCR-RFLP of p.I300L and p.F354S variants among 132 GD patients, 105 Hashimoto thyroiditis (HT), 206 Healthy subjects and 102 families with NSHL have shown the presence of both variants. The p.F354S variation was identified both among patients (1~HT and 3 GD) and healthy subjects (n=5). Whereas, the p.I300L variant was identified only in GD patients (n=3). Our studies provide evidence of the importance of systematic analysis of SLC26A4 gene sequences on models other than deafness. This approach allows the identification of new variants and the review of the pathogenic effects of certain mono-allelic variants reported responsible for PS and NSHL development.