Analysis of the SLC26A4 gene in patients with Pendred syndrome in Taiwan

Abstract Pendred syndrome (PS) is an autosomal recessive disease that is characterized by congenital sensorineural hearing loss, goiter, and a partial iodine organification defect. In this study, we characterized the thyroid status and identified mutations in the SLC26A4 gene in Chinese subjects with PS. We evaluated 7 unrelated Chinese subjects who had PS. Biochemical analysis, formal audiogram, ultrasonography of the thyroid gland, perchlorate discharge test, computerized tomography scan of the vestibular aqueducts, and DNA sequence analysis of SLC26A4 were performed. Levels of thyroid hormones were essentially normal in all patients: 2 patients had goiters and/or elevated serum thyroglobulin levels, whereas 2 other patients had positive thyroid antibodies and a positive perchlorate discharge test. We identified SLC26A4 gene mutations in 6 of 7 probands and their affected relatives. The affected subjects in family I was compound heterozygous for 2 missense mutations: a mutation in exon 9 (1079C>T) that resulted in the replacement of alanine by valine at codon 360 (A360V) and a mutation in exon 19 (2168A>G) that resulted in the replacement of histidine by arginine at codon 723 (H723R). The affected subjects in families II and III all were homozygous for a mutation in intron 7. The probands IV and V were compound heterozygotes for the mutation in intron 7 and in exon 19, and the proband VI was compound heterozygous for the intron 7 mutation and a missense mutation in exon 12 (1343C>T) that resulted in the replacement of serine by leucine at codon 448 (S448L). One novel mutation was identified (A360V). We identified biallelic mutations in the SLC26A4 gene in 6 of 7 probands with PS in Taiwan, including a novel missense mutation. The mild thyroid dysfunction in these patients suggests that PS should be considered in all patients with congenital or early-onset hearing impairment.