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Genomics and Hearing Loss: Toward a New Standard of Care?
Published in Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm, Advances in Audiology and Hearing Science, 2020
Transmembrane anion exchanger: The SLC26A4 gene encodes the pendrin protein, a transmembrane anion exchanger and is expressed in different tissues, including the thyroid, kidney and inner ear. Mutations in the pendrin gene are the second most frequent cause of autosomal recessive nonsyndromic hearing loss, accounting for up to 3.5% of cases (Hutchin et al., 2005). SLC26A4 also underlies Pendred syndrome, which is one of the most common autosomal recessive syndromic causes of hearing loss. In humans, enlargement of the vestibular aqueduct is present in almost all individuals with Pendred syndrome or DFNB4 deafness although an enlarged vestibular aqueduct can be present as an isolated finding along with sensorineural hearing loss. Mutations in SLC26A4 cause a spectrum of hearing loss, congenital or with a late onset, ranging from mild to profound, stable or progressive along the lifetime. Approximately half of the Pendred syndrome cases are caused by a mutation in SLC26A4.
Pendred Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The SLC26A4 (solute carrier family 26 member 4, or human pendrin polypeptide) gene on chromosome 7q22.3 spans 67 kb and encodes a 780 aa, 85 kDa anion transporter protein (pendrin) belonging to the SLC26 anion transporter family.
Genetics in Otology and Neurotology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
This is the second most common type of autosomal recessive syndromic hearing loss. It is usually characterized by severe congenital sensorineural hearing loss and euthyroid goitre that develops in puberty or adulthood. The deafness is also commonly associated with an abnormality of the labyrinth which may be anatomical (Mondini dysplasia or dilated vestibular aqueduct) and/or functional. Almost 50% of the families have SLC26A4 (PDS) gene mutation on chromosome 7q21-q34. The gene is responsible for sulfate transport. Its protein product, pendrin, is involved in the transport of iodine and chloride ions. SLC26A4 gene mutation should be investigated in the patients who have progressive hearing loss, Mondini dysplasia or large vestibular aqueduct syndrome. The same mutation can also cause DFNB4.29
Molecular screening of patients with profound hearing loss from Chengdu, China
Published in Acta Oto-Laryngologica, 2022
Qingqing Dai, Wei Dai, Dan Wang, Xia Liu, Ling Zou, Jiani Chen, Hong Zheng, Maoli Duan
The most common molecular defect in non-syndromic autosomal recessive deafness involves the GJB2 gene, which encodes Connexin 26, a gapjunction protein 6,7, and 235delC, the most frequent mutation in the Chinese population [6]. Defects in SLC26A4, which encodes the anion transporter pendrin, can cause non-syndromic DFNB4 deafness with enlargement of the vestibular aqueduct and Pendred syndrome [7]. Mutation of SLC26A4 is the second most common cause of deafness in China [8], and IVS7-2A > G is the common mutation [9]. Moreover, well-studied mutations related to aminoglycoside susceptibility are A1555G and C1494T in the mitochondrial 12SrRNA gene [10]. Non-syndromic inherited hearing loss caused by mutations in GJB2, SLC26A4, and mtDNA 12SrRNA accounts for 33.8% of all the deaf from Special Education School within China [8], and the hotspot mutation detection becomes a much more available method. Based on the large-scale epidemiological multi-center study data across 28 provinces and municipalities all over China, nine hot gene loci of four deaf-associated genes have been found in the Chinese population. Thus, we focus on detecting the nine hotspots simultaneously using microarray chip technology in inherited hearing loss [11].
The patient with metabolic alkalosis
Published in Acta Clinica Belgica, 2019
Valentine Gillion, Michel Jadoul, Olivier Devuyst, Jean-Michel Pochet
Recently, a protein called pendrin, a sodium-independent Cl-/HCO3- exchanger (Figure 1) localized on the apical membrane of type B intercalated cells in the distal nephron was identified [26]. This protein works with the neutral sodium-chloride cotransporter (NCC) to maintain sodium chloride balance and probably plays a key role in the secretion of bicarbonate to prevent the development of metabolic alkalosis. Studies in mutant mice show that pendrin and the NaCl cotransporter (SLC12A3) compensate for the loss of each other. Pendrin could also work with the sodium-dependent chloride/bicarbonate exchanger to mediate the reabsorption of NaCl. Patients with Pendred syndrome (SCL26A4; MIM # 274,600), a recessive disease resulting from mutations in pendrin, present developmental abnormalities of the cochlea with sensorineural hearing loss and diffuse thyroid enlargement or goiter. Pendrin is abundantly expressed in the thyroid and inner ear, with very low levels in the kidney. Patients with Pendred syndrome develop severe hypovolemia and metabolic alkalosis only when treated with thiazide diuretics.
A pathogenic variant in SLC26A4 is associated with Pendred syndrome in a consanguineous Iranian family
Published in International Journal of Audiology, 2019
Azam Pourahmadiyan, Paria Alipour, Najmeh Fattahi, Mahbubeh Kasiri, Fateme Rezaeian, Afsaneh Taghipour-Sheshdeh, Javad Mohammadi-Asl, Mohammad Amin Tabatabaiefar, Morteza Hashemzadeh Chaleshtori
SLC26A4 (OMIM: 605646) was identified by Everett et al. (1997) after using positional cloning on chromosome 7q22-31 (Hilgert, Smith, and Van Camp 2009). This gene consists of 21 exons (Everett et al. 1997) and produces a 5 kb transcript and a 86 kDa protein with 780 amino acids, pendrin, which is a member of solute carrier family 26A (SLC26A) (Bizhanova and Kopp 2010; Campbell et al. 2001). Pendrin mediates the transport of Cl−, HCO3−, OH−, I− ions, as well as formate, nitrate and thiocyanate. Reduction of pendrin level functionally results in endolymph acidification, and is thought to be responsible for inhibition of Ca2+ re-absorption, leading to auditory sensory transduction defects (Wangemann et al. 2007).