title: Screening of SLC26A4 gene in autoimmune thyroid diseases.
abstract: The Pendred syndrome (PS) gene, SLC26A4, was involved in the genetic susceptibility of autoimmune thyroid disease (AITD) in Tunisian population. Recently, functional assays have shown a differential expression of SLC26A4 gene between Graves' disease (GD) and Hashimoto's thyroiditis (HT). Here, by the mean of DHPLC and HRM, we explored the 21 exons and their flanking intronic sequences of 128 patients affected with GD (n = 64) or HT (n = 64). The pathogenic effect of identified variations on splice was investigated using the web server HSF. Eighteen allelic variations were identified and ranged on missense, sens and splice variations. Nine identified variations (c.-66C>G, c.898A>C, c.1002-9A>C, c.1061T>C, c.1544 + 9G>T, c.1545-5T>G, c.1790T>C, c.1826T>G, c.2139T>G) were previously reported in hearing impairment studies. Forty-seven per cent (30/64) of GD patients and 37,5% (24/64) of HT patients present at least one variant in the explored sequences. Moreover, the analysis of the variant distribution between HT (9 (5'UTR), 12 exonic and 13 intronic) and GD (18 (5'UTR), 13 exonic and 5 intronic) patients showed a significant difference (χ² = 6.54, 2df, P = 0.03). Interestingly, missense changes (I300L, p.M283I, F354S and p.L597S) affected conserved residues of pendrin. On the other hand, the HSF analyses ascertain that some variants identified in HT disease are predicted to have a pathogenic effect on splice. In conclusion, our analysis of SLC26A4 sequence variations suggested a distinct genetics basis between HT and GD patients, which should be confirmed on a large cohort.
authors.affiliation: Laboratoire de Microorganismes et Biomolécules, équipe des Procédés de Criblage Moléculaires et Cellulaires, Center de Biotechnologie de Sfax, Sfax, Tunisie.
authors.forename: R
authors.initials: R
authors.lastname: Kallel
authors.forename: M
authors.initials: M
authors.lastname: Niasme-Grare
authors.forename: S
authors.initials: S
authors.lastname: Belguith-Maalej
authors.forename: M
authors.initials: M
authors.lastname: Mnif
authors.forename: M
authors.initials: M
authors.lastname: Abid
authors.forename: H
authors.initials: H
authors.lastname: Ayadi
authors.forename: S
authors.initials: S
authors.lastname: Masmoudi
authors.forename: L
authors.initials: L
authors.lastname: Jonard
authors.forename: H
authors.initials: H
authors.lastname: Hadj Kacem
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006044:Goiter, Nodular / Q000235:genetics; D006111:Graves Disease / Q000235:genetics*; D050031:Hashimoto Disease / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020125:Mutation, Missense; D020033:Protein Isoforms / Q000235:genetics; D000076988:Sulfate Transporters; D014416:Tunisia
chemical_list: D026901:Membrane Transport Proteins; D020033:Protein Isoforms; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters