Title: MYH9-Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype-Phenotype Correlations
Authors: Pecci, Alessandro ×
Klersy, Catherine
Gresele, Paolo
Lee, Kieran J D
De Rocco, Daniela
Bozzi, Valeria
Russo, Giovanna
Heller, Paula G
Loffredo, Giuseppe
Ballmaier, Matthias
Fabris, Fabrizio
Beggiato, Eloise
Kahr, Walter H A
Pujol-Moix, Nuria
Platokouki, Helen
Van Geet, Chris
Noris, Patrizia
Yerram, Preethi
Hermans, Cedric
Gerber, Bernhard
Economou, Marina
De Groot, Marco
Zieger, Barbara
De Candia, Erica
Fraticelli, Vincenzo
Kersseboom, Rogier
Piccoli, Giorgina B
Zimmermann, Stefanie
Fierro, Tiziana
Glembotsky, Ana C
Vianello, Fabrizio
Zaninetti, Carlo
Nicchia, Elena
Güthner, Christiane
Baronci, Carlo
Seri, Marco
Knight, Peter J
Balduini, Carlo L
Savoia, Anna #
Issue Date: Feb-2014
Publisher: John Wiley & Sons, Inc.
Series Title: Human Mutation vol:35 issue:2 pages:236-47
Article number: 10.1002/humu.22476
Abstract: MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype-phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD.
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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