Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome.
Kidney Int
; 96(4): 883-889, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31472902
ABSTRACT
Steroid-resistant nephrotic syndrome is a frequent cause of chronic kidney disease almost inevitably progressing to end-stage renal disease. More than 58 monogenic causes of SRNS have been discovered and majority of known steroid-resistant nephrotic syndrome causing genes are predominantly expressed in glomerular podocytes, placing them at the center of disease pathogenesis. Herein, we describe two unrelated families with steroid-resistant nephrotic syndrome with homozygous mutations in the KIRREL1 gene. One mutation showed high frequency in the European population (minor allele frequency 0.0011) and this patient achieved complete remission following treatment, but later progressed to chronic kidney disease. We found that mutant KIRREL1 proteins failed to localize to the podocyte cell membrane, indicating defective trafficking and impaired podocytes function. Thus, the KIRREL1 gene product has an important role in modulating the integrity of the slit diaphragm and maintaining glomerular filtration function.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a Medicamentos
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Insuficiencia Renal Crónica
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Glucocorticoides
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Proteínas de la Membrana
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Síndrome Nefrótico
Tipo de estudio:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Kidney Int
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos