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Pathogenic variants in the Alport genes are prevalent in the Singapore multiethnic population with highest frequency in the Chinese.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Nephritis, Hereditary*/genetics ; Nephritis, Hereditary*/epidemiology ; Asian People*/genetics ; Collagen Type IV*/genetics ; Autoantigens*/genetics; Humans ; Singapore/epidemiology ; Male ; Prevalence ; Female ; Adult ; East Asian People
    • Abstract:
      Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
      Alport syndrome is a common monogenic kidney disease resulting from pathogenic variants in COL4A3, COL4A4 or COL4A5 genes. The estimated global population prevalence is one in 106 individuals for autosomal dominant (AD) and one in 2,320 for sex-linked (XL) conditions. Here, we aimed to estimate the population prevalence of individuals carrying pathogenic variants that cause Alport syndrome in Singapore, and to stratify the prevalence by ancestry. We used population-scale genomic data of 9,051 unrelated subjects, comprising 5,443 (60.8%) Chinese, 1,922 (21.4%) Indian and 1,686 (17.8%) Malay individuals. The prevalence of individuals with pathogenic variants that cause AD and XL Alport syndrome are 1 in 165 and 1 in 2,262 respectively. Additionally, 0.8% of Chinese and 0.3% of Malay populations carry pathogenic Alport syndrome variants, with Chinese individuals being 2.7 times more affected than Malays (95% CI:1.147-6.437, P = 0.027). Interestingly, each pathogenic variant was associated with people of a single ancestry. The two most prevalent pathogenic variants, COL4A3: c.3856G > A (p.Gly1286Arg) (n = 8) and COL4A3: c.4793T > G (p.Leu1598Arg) (n = 4), were exclusively found in the Chinese population. In conclusion, AD Alport syndrome may be prevalent in Singapore, with higher frequencies among the Chinese. Furthermore, founder effects may exist within the ancestries.
      (© 2025. The Author(s).)
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    • Grant Information:
      Health and Economic Impact of Next Generation Sequencing in Primary Glomerular Diseases in Singapore (PGD) Precision Health Research, Singapore; MOH-000588 Precision Health Research, Singapore
    • Accession Number:
      0 (Collagen Type IV)
      0 (type IV collagen alpha3 chain)
      0 (Autoantigens)
      0 (COL4A5 protein, human)
    • Publication Date:
      Date Created: 20250305 Date Completed: 20250511 Latest Revision: 20250511
    • Publication Date:
      20250512
    • Accession Number:
      PMC11883019
    • Accession Number:
      10.1038/s41598-025-92520-9
    • Accession Number:
      40044766