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Identification of a dysfunctional exon-skipping splice variant in GLUT9/SLC2A9 causal for renal hypouricemia type 2.

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F23%3AN0000037" target="_blank" >RIV/00023728:_____/23:N0000037 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11110/23:10458789 RIV/00064165:_____/23:10458789

  • Result on the web

    <a href="https://doi.org/10.3389/fgene.2022.1048330" target="_blank" >https://doi.org/10.3389/fgene.2022.1048330</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3389/fgene.2022.1048330" target="_blank" >10.3389/fgene.2022.1048330</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Identification of a dysfunctional exon-skipping splice variant in GLUT9/SLC2A9 causal for renal hypouricemia type 2.

  • Original language description

    Renal hypouricemia (RHUC) is a pathological condition characterized by extremely low serum urate and overexcretion of urate in the kidney; this inheritable disorder is classified into type 1 and type 2 based on causative genes encoding physiologically-important urate transporters, URAT1 and GLUT9, respectively; however, research on RHUC type 2 is still behind type 1. We herein describe a typical familial case of RHUC type 2 found in a Slovak family with severe hypouricemia and hyperuricosuria. Via clinico-genetic analyses including whole exome sequencing and in vitro functional assays, we identified an intronic GLUT9 variant, c.1419+1G>A, as the causal mutation that could lead the expression of p.Gly431GlufsTer28, a functionally-null variant resulting from exon 11 skipping. The causal relationship was also confirmed in another unrelated Macedonian family with mild hypouricemia. Accordingly, non-coding regions should be also kept in mind during genetic diagnosis for hypouricemia. Our findings provide a better pathogenic understanding of RHUC and pathophysiological importance of GLUT9.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30101 - Human genetics

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Frontiers in Genetics

  • ISSN

    1664-8021

  • e-ISSN

    1664-8021

  • Volume of the periodical

    13

  • Issue of the periodical within the volume

    Art. Nr. 1048330

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    10

  • Pages from-to

    1-10

  • UT code for WoS article

    000923716300001

  • EID of the result in the Scopus database

    2-s2.0-85147272661