title: MYH9-related disease: five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations.
abstract: 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.
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
authors.forename: Helen
authors.initials: H
authors.lastname: Platokouki
authors.forename: Paula G
authors.initials: PG
authors.lastname: Heller
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
authors.forename: Roberta
authors.initials: R
authors.lastname: Bottega
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Serena
authors.initials: S
authors.lastname: Barozzi
authors.forename: Ana C
authors.initials: AC
authors.lastname: Glembotsky
authors.forename: Helen
authors.initials: H
authors.lastname: Pergantou
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D011487:Protein Conformation; D016415:Sequence Alignment; D013577:Syndrome; D013921:Thrombocytopenia / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains