Thrombomodulin Gene Mutation and Associated Predisposing Factors in Familial Collapsing Glomerulopathy.

Autor:	Riguetti MTP; Department of Medicine, Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil., Varela-Calais P; Center for Research and Molecular Diagnostic of Genetic Diseases - Department of Biophysics, Federal University of Sao Paulo, São Paulo, Brazil.; McKusick-Nathans Institute of Genetic Medicine - Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Fernandes DE; Department of Medicine, Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil., da Silva Franco JF; Center for Research and Molecular Diagnostic of Genetic Diseases - Department of Biophysics, Federal University of Sao Paulo, São Paulo, Brazil., Ribeiro Nogueira B; Center for Research and Molecular Diagnostic of Genetic Diseases - Department of Biophysics, Federal University of Sao Paulo, São Paulo, Brazil., Pesquero JB; Center for Research and Molecular Diagnostic of Genetic Diseases - Department of Biophysics, Federal University of Sao Paulo, São Paulo, Brazil., Mastroianni-Kirsztajn G; Department of Medicine, Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Nephron [Nephron] 2024; Vol. 148 (7), pp. 508-514. Date of Electronic Publication: 2024 Feb 19.
DOI:	10.1159/000536244
Abstrakt:	Collapsing glomerulopathy (CG) is a rare glomerular disease and its familial form is even rarer. CG and non-collapsing forms of focal segmental glomerulosclerosis 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. We performed renal and etiological routine evaluation, PVB19 serology, genetic tests including whole-exome analysis and dosage of serum thrombomodulin (THBD) in two siblings with CG, one healthy sister, and their mother. 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. THBD levels were elevated in the serum of both affected siblings. They also had PVB19 positive serology and the G1 high-risk apolipoprotein L1 (APOL1) alleles in homozygosity. Their healthy sister had no PVB19-positive serology and no THBD nor APOL1 gene variants. 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 multihit 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. (© 2024 S. Karger AG, Basel.)
Databáze:	MEDLINE
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