IgA nephropathy (IgAN) represents the most common primary glomerulonephritis worldwide with a prevalence of 25-50% among patients with primary glomerulopathies. In similar to 5-10% of the patients the disease segregates with an autosomal dominant (AD) pattern. Association studies identified loci on chromosomes 1q32, 6p21, 8p23, 17p13, 22q12, whereas classical linkage studies on AD families identified loci on chromosomes 2q36, 4q26-31, 6q22, 17q12-22. We have studied a large Sicilian family where IgAN segregates with an AD transmission. To identify the causal gene, the exomes of two affected and one unaffected individual have been sequenced. From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation. Moreover, functional characterization of this variant showed that it is responsible for the inhibition of the MAPK/ERK1/2 pathway. The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.

Milillo, A., La Carpia, F., Costanzi, S., D'urbano, V., Martini, M., Lanuti, P., Vischini, G., Larocca, L., Marchisio, M., Miscia, S., Amoroso, A., Gurrieri, F., Sangiorgi, E., A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy, <<EUROPEAN JOURNAL OF HUMAN GENETICS>>, 2015; 23 (12): 1673-1678 [http://hdl.handle.net/10807/172655]

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy

Martini, M;Larocca, Lm;Gurrieri, F;Sangiorgi, E
2015

Abstract

IgA nephropathy (IgAN) represents the most common primary glomerulonephritis worldwide with a prevalence of 25-50% among patients with primary glomerulopathies. In similar to 5-10% of the patients the disease segregates with an autosomal dominant (AD) pattern. Association studies identified loci on chromosomes 1q32, 6p21, 8p23, 17p13, 22q12, whereas classical linkage studies on AD families identified loci on chromosomes 2q36, 4q26-31, 6q22, 17q12-22. We have studied a large Sicilian family where IgAN segregates with an AD transmission. To identify the causal gene, the exomes of two affected and one unaffected individual have been sequenced. From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation. Moreover, functional characterization of this variant showed that it is responsible for the inhibition of the MAPK/ERK1/2 pathway. The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.
Inglese
Milillo, A., La Carpia, F., Costanzi, S., D'urbano, V., Martini, M., Lanuti, P., Vischini, G., Larocca, L., Marchisio, M., Miscia, S., Amoroso, A., Gurrieri, F., Sangiorgi, E., A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy, <<EUROPEAN JOURNAL OF HUMAN GENETICS>>, 2015; 23 (12): 1673-1678 [http://hdl.handle.net/10807/172655]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/172655
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