Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population

Scientific paper - Original scientific paper

• Author: Matija Horaček
• Author: Tamara Nikuševa Martić
• Author: Petar Šenjug
• Author: Marija Šenjug Perica
• Author: Maja Oroz
• Author: Sania Kuzmac
• Author: Dragan Klarić
• Author: Merica Glavina Durdov
• Author: Marijan Saraga
• Author: Danko Milošević
• Author: Danica Batinić
• Author: Marijana Ćorić
• Author: Frane Paić
• Author: Danica Galešić Ljubanović
• Author's institution: University of Zagreb; School of Medicine; (Department of Medical Biology)
• Author's institution: University of Zagreb; School of Medicine; (Department of Pathology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology

Abstract (english)

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 – 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients.

• Keywords (english): Adult; Collagen Type IV / genetics; Croatia / epidemiology; Female; Glomerulosclerosis, Focal Segmental / epidemiology; Humans; Male; Middle Aged; Nephritis, Hereditary / genetics; Proteinuria / epidemiology
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Bosnian Journal of Basic Medical Sciences
• Numbering: vol. 23, no. 1, pp. 89-100
• p-ISSN: 1512-8601
• e-ISSN: 1840-4812
• DOI: https://doi.org/10.17305/bjbms.2022.7567
• URN:NBN: urn:nbn:hr:105:648455
• Publication: 2023-02-01
• Document URL: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7567
• Type of resource: Text
• Access conditions: Open access
• Created on: 2023-04-14 11:34:59