Pendred's syndrome results from bi-allelic pathogenic variants in the SLC26A4 gene and is characterized by sensorineural deafness and a partial thyroid iodine organification defect, with or without goiter. Vestibular dysfunction is occasionally present, although it is not part of the classic clinical definition of Pendred's syndrome. The pendrin protein, encoded by the SLC26A4 gene, is responsible for transporting anions across cell membranes, including in the inner ear and thyroid. In the ear, pendrin functions as a HCO-/Q" exchanger and has a key role in maintaining endolymph homeostasis. In the thyroid, pendrin function is still not clear, and efforts are being made to identify the molecular mechanisms that underlie the broad thyroid phenotypic variation of Pendred's patients. While environmental factors, such as an iodine-deficient diet, contribute to phenotypic heterogeneity, other strong genetics factors should be considered. Several mouse models bearing Slc26a4 mutations have been generated. Unique calcium oxalate minerals have been found in the vestibule of loop, a mouse model with a hypo-functional allele of Slc26a4. The abnormal mineralized bodies were detected ectopically within the vestibular labyrinth. The thyroids of Slc26a4loop/loop mice are small with atrophic follicles. In this chapter, we summarize the unique findings of Slc26a4loop/loop mice in the vestibular system and thyroid gland. The existence of phenotypic variation observed among different Slc26a4 mouse models is encouraging evidence for further investigating mutation-specific mechanisms for Pendred's syndrome. The ability to predict specific phenotypes for a given mutation will contribute to better clinical management and treatment, with an emphasis on preventive medicine.
|Title of host publication||The Role of Pendrin in Health and Disease|
|Subtitle of host publication||Molecular and Functional Aspects of the SLC26A4 Anion Exchanger|
|Publisher||Springer International Publishing|
|Number of pages||14|
|State||Published - 2 Mar 2017|