Detection of Cryptic Mosaicism in X-linked Alport Syndrome Prompts to Re-evaluate Living-donor Kidney Transplantation.
Transplantation
; 104(11): 2360-2364, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-31895869
ABSTRACT
BACKGROUND:
Alport syndrome is a hereditary nephropathy caused by mutations in collagen IV genes and characterized by ultrastructural lesions of the glomerular basement membrane. Some patients have a negative family history with apparently de novo mutations. Although somatic mosaicism has been postulated, as cryptic mosaicism cannot be detected from mutational screening on peripheral blood samples, cases in kidney-confined mosaic form have been missed.METHODS:
We report the case of a 24-year-old male patient with X-linked Alport syndrome diagnosis due to a COL4A5 pathogenic mutation (c.3334_3337dup [p.Gly1113Alafs25]). The same mutation had not been previously detected on a peripheral blood sample of maternal DNA. However, the mother, who was undertaking a clinical re-evaluation to take in consideration the possibility of a living-kidney transplantation, had experienced persistent microhematuria since the age of 10 years.RESULTS:
A next-generation sequencing approach performed on maternal DNA from both peripheral blood sample and urine-derived podocyte-lineage cells unmasked the COL4A5 mutation only in the podocyte-lineage cells.CONCLUSIONS:
This finding unveils an early postzygotic event which can explain both the renal involvement and germline mosaicism. It changes the inheritance risk for each pregnancy raising it to 50% and underlines the need for different clinical management in the mother. This seems to indicate that a case-by-case more cautious approach is needed with mother-to-son kidney transplants.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Riñón
/
Donadores Vivos
/
Colágeno Tipo IV
/
Cromosomas Humanos X
/
Mosaicismo
/
Mutación
/
Nefritis Hereditaria
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Transplantation
Año:
2020
Tipo del documento:
Article