학술논문
Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.
Document Type
Article
Author
Dorval, Guillaume; Gribouval, Olivier; Martinez-Barquero, Vanesa; Machuca, Eduardo; Tête, Marie-Josèphe; Baudouin, Véronique; Benoit, Stéphane; Chabchoub, Imen; Champion, Gérard; Chauveau, Dominique; Chehade, Hassib; Chouchane, Chokri; Cloarec, Sylvie; Cochat, Pierre; Dahan, Karin; Dantal, Jacques; Delmas, Yahsou; Deschênes, Georges; Dolhem, Phillippe; Durand, Dominique
Source
Subject
*NEPHROTIC syndrome
*GENETICS
*IMMUNITY
*GENETIC mutation
*SEQUENCE analysis
*GENOTYPES
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Language
ISSN
0931-041X
Abstract
Background: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease.Methods: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort.Results: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing.Conclusions: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance. [ABSTRACT FROM AUTHOR]