Next Article in Journal
Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate—Case Report
Previous Article in Journal
Comparing Door-To-Balloon Time between ST-Elevation Myocardial Infarction Electrocardiogram and Its Equivalents
 
 
Article

Molecular Features of SLC26A4 Common Variant p.L117F

1
Institute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, Austria
2
Department of Human Molecular Genetics & Biochemistry, Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel
3
Department of Otorhinolaryngology, Head and Neck Surgery, Paracelsus Medical University, 5020 Salzburg, Austria
*
Authors to whom correspondence should be addressed.
Academic Editor: Aziz El-Amraoui
J. Clin. Med. 2022, 11(19), 5549; https://doi.org/10.3390/jcm11195549
Received: 19 August 2022 / Revised: 16 September 2022 / Accepted: 19 September 2022 / Published: 22 September 2022
The SLC26A4 gene, which encodes the anion exchanger pendrin, is involved in determining syndromic (Pendred syndrome) and non-syndromic (DFNB4) autosomal recessive hearing loss. SLC26A4 c.349C>T, p.L117F is a relatively common allele in the Ashkenazi Jewish community, where its minor allele frequency is increased compared to other populations. Although segregation and allelic data support the pathogenicity of this variant, former functional tests showed characteristics that were indistinguishable from those of the wild-type protein. Here, we applied a triad of cell-based assays, i.e., measurement of the ion transport activity by a fluorometric method, determination of the subcellular localization by confocal microscopy, and assessment of protein expression levels, to conclusively assign or exclude the pathogenicity of SLC26A4 p.L117F. This protein variant showed a moderate, but significant, reduction in ion transport function, a partial retention in the endoplasmic reticulum, and a strong reduction in expression levels as a consequence of an accelerated degradation by the Ubiquitin Proteasome System, all supporting pathogenicity. The functional and molecular features of human pendrin p.L117F were recapitulated by the mouse ortholog, thus indicating that a mouse carrying this variant might represent a good model of Pendred syndrome/DFNB4. View Full-Text
Keywords: hearing loss; SLC26A4; pendrin; DFNB4; Pendred syndrome; functional testing hearing loss; SLC26A4; pendrin; DFNB4; Pendred syndrome; functional testing
Show Figures

Figure 1

MDPI and ACS Style

Matulevičius, A.; Bernardinelli, E.; Brownstein, Z.; Roesch, S.; Avraham, K.B.; Dossena, S. Molecular Features of SLC26A4 Common Variant p.L117F. J. Clin. Med. 2022, 11, 5549. https://doi.org/10.3390/jcm11195549

AMA Style

Matulevičius A, Bernardinelli E, Brownstein Z, Roesch S, Avraham KB, Dossena S. Molecular Features of SLC26A4 Common Variant p.L117F. Journal of Clinical Medicine. 2022; 11(19):5549. https://doi.org/10.3390/jcm11195549

Chicago/Turabian Style

Matulevičius, Arnoldas, Emanuele Bernardinelli, Zippora Brownstein, Sebastian Roesch, Karen B. Avraham, and Silvia Dossena. 2022. "Molecular Features of SLC26A4 Common Variant p.L117F" Journal of Clinical Medicine 11, no. 19: 5549. https://doi.org/10.3390/jcm11195549

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop