Clinical and pathohistological characteristics of Alport spectrum disorder caused by COL4A4 mutation c.193-2A>C: a case series

Scientific paper - Original scientific paper

• Author: Petar Šenjug
• Author: Tamara Nikuševa Martić
• Author: Marija Šenjug Perica
• Author: Maja Oroz
• Author: Matija Horaček
• Author: Kristina Gotovac Jerčić
• Author: Krešimir Galešić
• Author: Danica Galešić Ljubanović
• Author's institution: University of Zagreb; School of Medicine; (Department of Internal Medicine)
• Author's institution: University of Zagreb; School of Medicine; (Department of Pathology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology

Abstract (english)

Aim To present the pathohistological and clinical characteristics of five Croatian families with Alport spectrum disorders caused by splice acceptor pathogenic variant c.193-
2A>C in COL4A4 at the genomic position chr2:227985866. -----
Methods The study enrolled five probands with kidney biopsy analysis and five family members. Mutation screening
was performed with Illumina MiSeq platform. The pathogenic variant was confirmed with standard dye-terminator
sequencing.-----
Results The only homozygous patient, aged two, had proteinuria and hematuria with preserved kidney function
and no extrarenal manifestations. This patient had changes characteristic for Alport syndrome observed on electron microscopy of the kidney biopsy. In the heterozygous
group, six patients had hematuria, four biopsied probands
had proteinuria, and only one had moderately reduced
kidney function. Heterozygous probands had variable kidney biopsy findings. Three patients had thin glomerular
basement membrane nephropathy visible on electron microscopy and focal segmental glomerulosclerosis on light
microscopy, two of them with focal lamellation on electron microscopy. One heterozygous patient had changes
characteristic for Alport syndrome on electron microscopy
without focal segmental glomerulosclerosis. -----
Conclusion The homozygous patient had hematuria and
proteinuria with preserved kidney function. The heterozygous patients presented with reasonably mild clinical phenotype and variable pathohistological findings.

• Keywords (english): Collagen Type IV* / genetics; Hematuria / genetics; Humans; Mutation; Nephritis, Hereditary* / diagnosis; Nephritis, Hereditary* / genetics; Pedigree
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Croatian Medical Journal
• Numbering: vol. 62, no. 3, pp. 204-214
• p-ISSN: 0353-9504
• e-ISSN: 1332-8166
• DOI: https://doi.org/10.3325/cmj.2021.62.204
• URN:NBN: urn:nbn:hr:105:599310
• Publication: 2021-06-30
• Document URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275942/
• Type of resource: Text
• Access conditions: Open access
• Created on: 2021-07-28 07:30:58