All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid.
Chloride uptake studies were made using HEK293-Phoenix cells expressing human wild type SLC26A4 (pendrin) and a mutant (SLC26A4(S28R)) we recently described in a patient with hypothyroidism, goiter and sensorineural hearing loss.
Slc26a4 (-/-) and (+/+) mice were fed up to 6 months on a standard or low iodine diet and were evaluated for thyroid structural abnormalities or biochemical hypothyroidism.
We describe a 46-year-old female with sensorineural deafness and hypothyroidism, who presented with severe hypokalaemic metabolic alkalosis during inter-current illnesses on two occasions, and who was found to be homozygous for a loss-of-function mutation (V138F) in SLC26A4.
We propose using a combination of three parameters to define and diagnose PS: (i) sensorineural deafness with bilateral EVA; (ii) thyroid abnormality comprising goiter and/or hypothyroidism and/or a positive PDT; (iii) biallelic SLC26A4 mutations.
Therefore, present study reports for the first time that the observed novel variants in pendrin gene might be linked with autoimmune negative hypothyroidism, without any characteristics of Pendred syndrome and/or congenital hypothyroidism.