SLC26A4 variations among Graves' hyper-functioning thyroid gland.
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.
Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax, Tunisie. hassen.hadjkacem@cbs.rnrt.tn
Hassen
H
Hadj-Kacem
Rihab
R
Kallel
Salima
S
Belguith-Maalej
Mouna
M
Mnif
Ilhem
I
Charfeddine
Abdelmounem
A
Ghorbel
Mohamed
M
Abid
Hammadi
H
Ayadi
Saber
S
Masmoudi
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D006044:Goiter, Nodular / Q000235:genetics / Q000473:pathology; D006111:Graves Disease / Q000235:genetics* / Q000473:pathology; D050031:Hashimoto Disease / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation; D016415:Sequence Alignment; D000076988:Sulfate Transporters
D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters