Premium
Screening of SLC 26A4 gene in autoimmune thyroid diseases
Author(s) -
Kallel R.,
NiasmeGrare M.,
BelguithMaalej S.,
Mnif M.,
Abid M.,
Ayadi H.,
Masmoudi S.,
Jonard L.,
Hadj Kacem H.
Publication year - 2013
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12035
Subject(s) - missense mutation , exon , thyroiditis , rna splicing , genetics , thyroid , allele , gene , biology , graves' disease , intron , gene isoform , population , microbiology and biotechnology , splice , medicine , mutation , rna , environmental health
Summary The Pendred syndrome ( PS ) gene, SLC 26A4 , was involved in the genetic susceptibility of autoimmune thyroid disease ( AITD ) in Tunisian population. Recently, functional assays have shown a differential expression of SLC 26A4 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 SLC 26A4 sequence variations suggested a distinct genetics basis between HT and GD patients, which should be confirmed on a large cohort.