RESUMO
INTRODUCTION: Collapsing glomerulopathy (CG) is a rare glomerular disease and its familial form is even rarer. CG and non-collapsing forms of focal segmental glomerulosclerosis (FSGS) may both be caused by pathogenic variants in the same genes, but there is less information on genetics of the former disease. We hypothesized that different hits (viral infection and genetic variants) may be involved in the development of a familial CG here described. METHODS: Renal and etiological routine evaluation, PVB19 serology, genetic tests including whole exome analysis and dosage of serum thrombomodulin (THBD) were performed in two siblings with CG, one healthy sister and their mother. RESULTS: The THBD gene variant p.A43T in homozygosity was identified in the proband and her affected brother, both with CG. The same mutation was identified in their mother in heterozygosity. Thrombomodulin levels were elevated in the serum of both affected siblings. They also had PVB19 positive serology and the G1 high-risk apolipoprotein L1 (APOL1) alelles in homozygosity. Their healthy sister had no PVB19 positive serology and no THBD nor APOL1 gene variants. CONCLUSION: In this case of familial CG, THBD and APOL1 gene variants, and a previous PVB19 infection may be associated with the development of CG in a multi-hit process. In addition, the p.A43T THBD variant, identified in the affected siblings, has never been previously described in homozygosis, pointing to a likely autosomal recessive CG trait caused by this gene mutation.
