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Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.

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; Ekinci, Zelal; El Karoui, Khalil; Fischbach, Michel; Grunfeld, Jean-Pierre; Guigonis, Vincent; Hachicha, Mongia; Hogan, Julien; Hourmant, Maryvonne; Hummel, Aurélie; Kamar, Nassim; Krummel, Thierry; Lacombe, Didier; Llanas, Brigitte; Mesnard, Laurent; Mohsin, Nabil; Niaudet, Patrick; Nivet, Hubert; Parvex, Paloma; Pietrement, Christine; de Pontual, Loic; Noble, Claire Pouteil; Ribes, David; Ronco, Pierre; Rondeau, Eric; Sallee, Marion; Tsimaratos, Michel; Ulinski, Tim; Salomon, Rémi; Antignac, Corinne; Boyer, Olivia.
Pediatr Nephrol; 33(3): 473-483, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29058154

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.
Selo DaSilva