X-linked Alport syndrome presenting in mother and son with the same unique histopathological features.

Autor: Bergeron NAD; Service of Nephrology, L'Hôtel-Dieu de Québec Research Center, CHU de Québec-Université Laval, 10 McMahon Street (Room 3852), Québec, QC, G1R 2J6, Canada., Garneau AP; Service de Néphrologie-Transplantation Rénale Adultes, Hôpital Necker-Enfants Malades, AP-HP, Inserm U1151, Université Paris Cité, Rue de Sèvres, Paris, France., Rousseau-Gagnon M; Service of Nephrology, L'Hôtel-Dieu de Québec Research Center, CHU de Québec-Université Laval, 10 McMahon Street (Room 3852), Québec, QC, G1R 2J6, Canada., Riopel J; Service of Pathology, CHU de Québec-Université Laval, Québec, QC, G1R 2J6, Canada., Isenring P; Service of Nephrology, L'Hôtel-Dieu de Québec Research Center, CHU de Québec-Université Laval, 10 McMahon Street (Room 3852), Québec, QC, G1R 2J6, Canada. paul.isenring@crhdq.ulaval.ca.
Jazyk: angličtina
Zdroj: Journal of nephrology [J Nephrol] 2024 Apr; Vol. 37 (3), pp. 769-772. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1007/s40620-024-01942-7
Abstrakt: Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4 and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman's capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman's capsule is more vulnerable to missense mutations in COL4A5 than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: