Atypical focal segmental glomerulosclerosis associated with a new PODXL nonsense variant.
Mol Genet Genomic Med
; 9(5): e1658, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33780168
ABSTRACT
BACKGROUND:
Podocalyxin (PODXL) is a highly sialylated adhesion glycoprotein that plays an important role in podocyte's physiology. Recently, missense and nonsense dominant variants in the PODXL gene have been associated with focal segmental glomerulosclerosis (FSGS), a leading cause of nephrotic syndrome and kidney failure. Their histologic description, however, was superficial or absent.METHODS:
We performed exome sequencing on a three-generation family affected by an atypical glomerular nephropathy and characterized the disease by light and electron microscopy.RESULTS:
The disease was characterized by FSGS features and glomerular basement membrane duplication. Six family members displayed chronic proteinuria, ranging from mild manifestations without renal failure, to severe forms with end-stage renal disease. Exome sequencing of affected twin sisters, their affected mother, healthy father, and healthy maternal uncle revealed a new nonsense variant cosegregating with the disease (c.1453C>T, NM_001018111) in the PODXL gene, which is known to be expressed in the kidney and to cause nephropathy when mutated. The variant is predicted to lead to a premature stop codon (p.Q485*) that results in the loss of the intracytoplasmic tail of the protein.CONCLUSION:
This is the first description of a peculiar association combining a PODXL stop-gain variant and both FSGS and membranoproliferative glomerulonephritis features, described by light and electron microscopy.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sialoglicoproteínas
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Glomeruloesclerosis Focal y Segmentaria
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Codón sin Sentido
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Genet Genomic Med
Año:
2021
Tipo del documento:
Article
País de afiliación:
Francia