SLC26A4 variations among Graves' hyper-functioning thyroid gland.

[pendred syndrome]

Deleterious mutations of SLC 26 A 4 cause Pendred syndrome (PS ), an autosomal recessive disorder comprising goitre and deafness with enlarged vestibular aqueducts (EVA ), and nonsyndromic hearing loss (NSHL ). However , the SLC 26 A 4 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 SLC 26 A 4 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 .898 A >C (p .I 300 L ) and c .1061 T >C (p .F 3 54 S ), of the three exonic variants are non synonymous . The p .F 3 54 S variant is already described to be involved in PS or NSHL inheritances . The exploration by PCR-RFLP of p .I 300 L and p .F 3 54 S 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 .F 3 54 S variation was identified both among patients (1 ~HT and 3 GD ) and healthy subjects (n =5 ). Whereas , the p .I 300 L variant was identified only in GD patients (n =3 ). Our studies provide evidence of the importance of systematic analysis of SLC 26 A 4 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 .

Diseases
Validation

Diseases presenting "hearing loss" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

benign recurrent intrahepatic cholestasis

canavan disease

cohen syndrome

congenital toxoplasmosis

dentinogenesis imperfecta

fabry disease

familial mediterranean fever

heparin-induced thrombocytopenia

hirschsprung disease

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

neonatal adrenoleukodystrophy

pendred syndrome

von hippel-lindau disease

wolf-hirschhorn syndrome

This symptom has already been validated