رسالة جامعية
Pathogenicity Assessment of Pendrin (SLC26A4) Variants ; Pendrino (SLC26A4) variantų patogeniškumo nustatymas
| العنوان: | Pathogenicity Assessment of Pendrin (SLC26A4) Variants ; Pendrino (SLC26A4) variantų patogeniškumo nustatymas |
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| المؤلفون: | Jamontas, Rapolas |
| المساهمون: | Urbonavičius, Jaunius |
| بيانات النشر: | Institutional Repository of Vilnius Gediminas Technical University |
| سنة النشر: | 2020 |
| المجموعة: | LAEI VL (Lithuanian Institute of Agrarian Economics Virtual Library) / LAEI VB (Lietuvos agrarinės ekonomikos institutasvirtualią biblioteką) |
| مصطلحات موضوعية: | pendrin, SLC26A4, anion exchanger, protein variants |
| الوصف: | The SLC26A4 gene encodes a protein (pendrin, SLC26A4), which is essential for the proper development and function of the inner ear. SLC26A4 sequence alterations give rise to two forms of inherited hearing loss that are the Pendred syndrome and the autosomal recessive deafness DFNB4. These clinical entities are characterized by hearing loss associated with a specific malformation of the inner ear, the enlarged vestibular aqueduct (EVA). However, EVA can be caused by factors unrelated to SLC26A4. Therefore, sequencing of the SLC26A4 gene and assessment of the potential pathogenicity of the protein variants found, are necessary to give a conclusive diagnosis of Pendred syndrome or DFNB4. This study focused on five SLC26A4 protein variants (p.Q101R, p.I136N, p.L597S, p.A664V and p.G740V) found in four patients from the first cohort with hearing loss and EVA recruited in Austria. Of these variants, two (p.Q101R and p.I136N) were novel and for all of them the pathogenicity was not unequivocally established in former studies. The possible pathogenicity of these variants was assessed by measurement of their ion transport activities using a fluorometric method and determination of the cellular expression levels by confocal microscopy. Four of these variants (p.Q101R, p.I136N, p.L597S and p.A664V) demonstrated impaired function and reduced expression levels, consistent with a pathogenic potential, whereas one (p.G740V) showed unaltered features compared to the wild type protein. These findings led to a conclusive identification of SLC26A4 being the causative gene in two patients with hearing loss. The strong positive correlation between ion transport and expression levels indicates that reduction of expression is the main feature leading to loss of function of SLC26A4 variants. |
| نوع الوثيقة: | master thesis |
| وصف الملف: | application/pdf |
| اللغة: | Lithuanian English |
| العلاقة: | http://vgtu.oai.elaba.lt/documents/38856962.pdfTest; http://vgtu.lvb.lt/VGTU:ELABAETD38856962&prefLang=en_USTest |
| الإتاحة: | http://vgtu.oai.elaba.lt/documents/38856962.pdfTest http://vgtu.lvb.lt/VGTU:ELABAETD38856962&prefLang=en_USTest |
| حقوق: | info:eu-repo/semantics/embargoedAccess |
| رقم الانضمام: | edsbas.5C6E7905 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |