Phospholipase C-Gamma 2 Activity in Familial Steroid-Sensitive Nephrotic Syndrome.
Pediatr Res
; 85(5): 719-723, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30568185
ABSTRACT
BACKGROUND:
Familial Steroid-sensitive Nephrotic Syndrome (SSNS) is rare, complicating the identification of candidate genes. A recent population-based approach study of SSNS identified HLA-DQA1 and Phospholipase C-Gamma 2 (PLCG2) missense coding variants as candidate loci. PLCG2 is a signaling molecule regulated by phosphorylation and is critical for Ca2+ flux in cells of the immune system.METHODS:
In order to detect a candidate gene for familial SSNS, we conducted an whole-exome sequencing in a pedigree consisting of two healthy parents, two non-identical twin brothers with SSNS, and a healthy young sibling. Flow cytometric assays were conducted to investigate the effects of the identified PLCG2 rare variants on B cell receptor-mediated PLCG2 tyrosine 759 phosphorylation, as well as on Ca2+ flux.RESULTS:
Two missense rare variants in the PLCG2 gene were detected in the affected twins. An increase in tyrosine phosphorylation of PLCG2 as well as more rapid Ca2+ flux were noted in response to stimulation in the affected twins compared to their parents.CONCLUSIONS:
Rare variants in PLCG2 segregated with disease in familial SSNS. Functional studies suggest the combined rare variants result in a gain of function in PLCG2 activity. Taken together, these results support PLCG2 as a possible candidate locus for familial SSNS.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Esteroides
/
Mutação de Sentido Incorreto
/
Fosfolipase C gama
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Síndrome Nefrótica
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article