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

Authors

  • Matija Horaček Institute of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia https://orcid.org/0000-0001-7491-3791
  • Tamara Nikuševa Martić Department of Medical Biology and Genetics, School of Medicine, University of Zagreb, Zagreb, Croatia
  • Petar Šenjug Department of Nephropatology and Electron Microscopy, Dubrava University Hospital, Zagreb, Croatia
  • Marija Šenjug Perica Division of Rheumatology, Srebrnjak Children’s Hospital, Zagreb, Croatia
  • Maja Oroz Department of Gynecology and Obstetrics, Clinical Hospital “Sveti Duh”, Zagreb, Croatia https://orcid.org/0000-0003-0639-7320
  • Sania Kuzmac Clinical Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia
  • Dragan Klarić Department of Nephrology, General Hospital Zadar, Zadar, Croatia https://orcid.org/0000-0002-1484-877X
  • Merica Glavina Durdov Department of Pathology, University Hospital Split, Split, Croatia
  • Marijan Saraga Department of Pediatrics, University Hospital Split, Split, Croatia https://orcid.org/0000-0002-6855-163X
  • Danko Milošević Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia https://orcid.org/0000-0003-3877-5824
  • Danica Batinić Pediatric ordination dr. Danica Batinić, Zagreb, Croatia
  • Marijana Ćorić Institute of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia; Clinical Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia https://orcid.org/0000-0001-7887-4101
  • Frane Paić Department of Medical Biology and Genetics, School of Medicine, University of Zagreb, Zagreb, Croatia; Laboratory for Epigenetics and Molecular medicine, School of Medicine Zagreb, Croatia https://orcid.org/0000-0001-9688-8582
  • Danica Galešić Ljubanović Institute of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia; Department of Nephropatology and Electron Microscopy, Dubrava University Hospital, Zagreb, Croatia https://orcid.org/0000-0002-2850-6316

DOI:

https://doi.org/10.17305/bjbms.2022.7567

Keywords:

Alport syndrome, thin basement membrane nephropathy, proteinuria, collagen type IV, α3 chain of collagen IV, COL4A3 c.2881 1G>A variant, targeted next-generation sequencing

Abstract

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.

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

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Published

2022-07-19

How to Cite

1.
Horaček M, Nikuševa Martić T, Šenjug P, Šenjug Perica M, Oroz M, Kuzmac S, Klarić D, Glavina Durdov M, Saraga M, Milošević D, Batinić D, Ćorić M, Paić F, Galešić Ljubanović D. Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population. Bosn J of Basic Med Sci [Internet]. 2022Jul.19 [cited 2022Dec.6];. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/7567

Issue

Section

Pathology