Slc26a4, encoding pendrin, is a member of the SLC26A transporter family. It functions as a transmembrane exchanger of anions and bases, transporting various ions like bicarbonate, chloride, iodine, and oxalate. This gene is expressed in multiple tissues such as the airway epithelium, kidney, thyroid, and is crucial for maintaining hearing function, renal function, blood pressure, and hormone and pH regulation [2,3].

Mutations in Slc26a4 are a common cause of deafness, responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum varies among ethnic groups. In a Chinese study, the ratio of EVA in the deaf population was at least 11% [1]. Functional studies on its variants showed most led to pendrin retention in the intracellular region and reduced transport capability [1]. Some patients with only one detectable mutant allele (M1) of Slc26a4 also have EVA, and in European-Caucasian M1 patients, a specific haplotype (CEVA) acts as a pathogenic recessive allele in trans to coding region or splice-site mutations [2].

In conclusion, Slc26a4 is essential for normal inner ear function and other physiological processes. Research on its mutations and functions, often through in-vivo studies on related phenotypes, has provided valuable insights into the genetic architecture of hearing loss. Understanding Slc26a4 is crucial for genetic diagnosis, counseling, prenatal testing, and pre-implantation diagnosis in EVA families [1,2].

References:

1. Yuan, Yongyi, Guo, Weiwei, Tang, Jie, He, David Z Z, Dai, Pu. 2012. Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China. In PloS one, 7, e49984. doi:10.1371/journal.pone.0049984. https://pubmed.ncbi.nlm.nih.gov/23185506/

2. Honda, Keiji, Griffith, Andrew J. 2021. Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss. In Human genetics, 141, 455-464. doi:10.1007/s00439-021-02311-1. https://pubmed.ncbi.nlm.nih.gov/34345941/

3. Lee, Dongun, Hong, Jeong Hee. 2024. Chloride/Multiple Anion Exchanger SLC26A Family: Systemic Roles of SLC26A4 in Various Organs. In International journal of molecular sciences, 25, . doi:10.3390/ijms25084190. https://pubmed.ncbi.nlm.nih.gov/38673775/