Affiliations: Unité Cibles pour le Diagnostic et la
Thérapie, Centre de Biotechnologie de Sfax, Tunisie | Service d'Endocrinology, CHU Hédi Chaker, Sfax,
Tunisie | Service d'ORL, CHU Habib Bourguiba, Sfax,
Tunisie
Note: [] Corresponding author: Dr. Hassen Hadj Kacem, Unité Cibles
pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax.
Route Sidi Mansour Km 6. BP "1177", 3018, Sfax, Tunisia. Tel.: +216 74 871 816;
Fax: +216 74 875 818; E-mail: [email protected]
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.
