MYH9-related disease: Five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations

MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated w...

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Detalles Bibliográficos
Autores: de Rocco, Daniela, Zieger, Barbara, Platokouki, Helen, Heller, Paula Graciela, Pastore, Annalisa, Bottega, Roberta, Noris, Patrizia, Barozzi, Serena, Glembotsky, Ana Claudia, Pergantou, Helen, Balduini, Carlo L., Savoia, Anna, Pecci, Alessandro
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/15005
Acceso en línea:http://hdl.handle.net/11336/15005
Access Level:acceso abierto
Palabra clave:MYH9 related disease
MYH9 gene
Mutational screening
Missense mutation
In frame deletion/duplication
Genotype-phenotype correlation
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Descripción
Sumario:MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain.