Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife - Publication - Bridge of Knowledge

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Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife

Abstract

A study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.Gly624Asp (G624D) in COL4A5 was predominant and accounted for 39% of Xlinked Alport Syndrome in unrelated Polish families (44 of 113). To evaluate its origins, the genetic variation in a 2.79 Mb segment encompassing the COL4A5 locus on chromosome X was assessed. All G624D alleles were found on the same rare haplotype background, indicating a founder effect dating back to the 12-13th century. The phenotypic data of 131 children with X-linked Alport Syndrome and their 195 affected adult relatives revealed that the G624D variant was associated with a significantly milder clinical course in comparison to other pathogenic COL4A5 variants. Furthermore the clinical course of this genetically uniform cohort was milder than that observed in individuals with other COL4A5 missense mutations. In spite of the benign clinical manifestation throughout childhood and early adulthood, the G624D variant confers significant risk for both kidney failure and deafness in males, albeit 20-30 years later than that observed in individuals with other COL4A5 pathogenic variants (50% cumulative risk of starting dialysis at 54 years (95% confidence interval: 50-62) v. 26 years (95% confidence interval: 22-30)). Thus, males with G624D are candidates for existing and emerging therapies for Alport Syndrome.

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Authors (28)

  • Photo of  Aleksandra M. Żurowska

    Aleksandra M. Żurowska

  • Photo of  Olga Bielska

    Olga Bielska

  • Photo of  Patrycja Daca-Roszak

    Patrycja Daca-Roszak

  • Photo of  Maciej Jankowski

    Maciej Jankowski

  • Photo of  Maria Szczepańska

    Maria Szczepańska

  • Photo of  Dagmara Roszkowska-Bjanid

    Dagmara Roszkowska-Bjanid

  • Photo of  Elżbieta Kuźma-Mroczkowska

    Elżbieta Kuźma-Mroczkowska

  • Photo of  Małgorzata Pańczyk-Tomaszewska

    Małgorzata Pańczyk-Tomaszewska

  • Photo of  Anna Moczulska

    Anna Moczulska

  • Photo of  Dorota Drożdż

    Dorota Drożdż

  • Photo of  Despina Hadjipanagi

    Despina Hadjipanagi

  • Photo of  Constantinos Deltas

    Constantinos Deltas

  • Photo of  Danuta Ostalska-Nowicka

    Danuta Ostalska-Nowicka

  • Photo of  Alina Rabiega

    Alina Rabiega

  • Photo of  Janina Taraszkiewicz

    Janina Taraszkiewicz

  • Photo of  Katarzyna Taranta-Janusz

    Katarzyna Taranta-Janusz

  • Photo of  Anna Wieczorkiewicz-Plaza

    Anna Wieczorkiewicz-Plaza

  • Photo of  Katarzyna Jobs

    Katarzyna Jobs

  • Photo of  Judyta Mews

    Judyta Mews

  • Photo of  Kinga Musiał

    Kinga Musiał

  • Photo of  Anna Jakubowska

    Anna Jakubowska

  • Photo of  Hanna Nosek

    Hanna Nosek

  • Photo of  Anna E. Jander

    Anna E. Jander

  • Photo of  Constantina Koutsofti

    Constantina Koutsofti

  • Photo of  Dominka Kuleszo

    Dominka Kuleszo

  • Photo of  Ewa Ziętkiewicz

    Ewa Ziętkiewicz

  • Photo of  Beata S. Lipska-Ziętkiewicz

    Beata S. Lipska-Ziętkiewicz

Keywords

Details

Category:
Articles
Type:
artykuły w czasopismach
Published in:
KIDNEY INTERNATIONAL no. 99, pages 1451 - 1458,
ISSN: 0085-2538
Language:
English
Publication year:
2021
Bibliographic description:
Żurowska A. M., Bielska O., Daca-Roszak P., Jankowski M., Szczepańska M., Roszkowska-Bjanid D., Kuźma-Mroczkowska E., Pańczyk-Tomaszewska M., Moczulska A., Drożdż D., Hadjipanagi D., Deltas C., Ostalska-Nowicka D., Rabiega A., Taraszkiewicz J., Taranta-Janusz K., Wieczorkiewicz-Plaza A., Jobs K., Mews J., Musiał K., Jakubowska A., Nosek H., Jander A. E., Koutsofti C., Stanisławska-Sachadyn A., Kuleszo D., Ziętkiewicz E., Lipska-Ziętkiewicz B. S.: Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife// KIDNEY INTERNATIONAL -Vol. 99,iss. 6 (2021), s.1451-1458
DOI:
Digital Object Identifier (open in new tab) 10.1016/j.kint.2020.10.040
Verified by:
Gdańsk University of Technology

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