Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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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
Аннотация
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.