title: R705H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17.
abstract: MYH9-related disease (MYH9-RD) is a rare autosomal dominant disease caused by mutation of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). MYH9-RD patients have macrothrombocytopenia and granulocyte inclusions (pathognomonic sign of the disease) containing wild-type and mutant NMMHC-IIA. During life they might develop sensorineural hearing loss, cataract, glomerulonephritis, and elevation of liver enzymes. One of the MYH9 mutations, p.R705H, was previously reported to be associated with DFNA17, an autosomal dominant non-syndromic sensorineural hearing loss without any other features associated. We identified the same mutation in two unrelated families, whose four affected individuals had not only hearing impairment but also thrombocytopenia, giant platelets, leukocyte inclusions, as well as mild to moderate elevation of some liver enzymes. Our data suggest that DFNA17 should not be a separate genetic entity but part of the wide phenotypic spectrum of MYH9-RD characterized by congenital hematological manifestations and variable penetrance and expressivity of the extra-hematological features.
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Verver
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pecci
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: D
authors.initials: D
authors.lastname: De Rocco
authors.affiliation: Clinic for Hematology, Oncology and Stem Cell Transplantation, Hospital for Children and Adolescent Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Ryhänen
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Barozzi
authors.affiliation: Radboud university medical center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Kunst
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Topsakal
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.|Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Savoia
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013921:Thrombocytopenia / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains
keywords: DFNA17 non-syndromic sensorineural hearing loss; MYH9-related disease; macrothrombocytopenia; p.R705H mutation