Hội chứng Alport liên kết nhiễm sắc thể X do biến thể COL4A5 c.1826G>A (p.Gly609Asp): Báo cáo ca lâm sàng và phân tích di truyền

Abstract

Introduction: X-linked Alport syndrome (XLAS) caused by mutations in the COL4A5 gene is the most common hereditary kidney disease affecting young males, with a broad spectrum of clinical manifestations ranging from isolated hematuria to end-stage renal disease. Next-generation sequencing (NGS) is increasingly being applied to detect novel variants, particularly in Vietnamese healthcare facilities. Case presentation: The patient is a male born in 2007, the second child in the family, with a healthy older brother. He was found to carry a hemizygous variant in COL4A5 (NM_033380.3: c.1826G>A, p.Gly609Asp), a highly conserved glycine-to-aspartate substitution within the Gly-X-Y motif of the collagenous domain. This variant has not been previously classified in ClinVar and was assessed as likely pathogenic according to ACMG/AMP criteria (PM1+PM2+PP3+PP4). Discussion: NGS panel testing for glomerular diseases in a male patient with early-onset nephrotic syndrome, hematuria, and steroid resistance helps distinguish idiopathic nephrotic syndrome from hereditary kidney diseases such as Alport syndrome. Early initiation and maintenance of maximum tolerated doses of renin-angiotensin system inhibitors (ACEi/ARB) represent a core strategy to delay end-stage renal disease. Identification of the COL4A5 p.Gly609Asp variant provides a basis for screening female family members and offering reproductive options counseling. Conclusion: This case confirms the value of NGS panel testing in the differential diagnosis of childhood nephrotic syndrome. Detection of the COL4A5 c.1826G>A variant enables determination of the genetic etiology, avoids unnecessary immunosuppressive therapy, guides kidney preservation strategies, and facilitates family genetic counseling.