title: Late onset and high-frequency dominant hearing loss in a family with MYH9 disorder.
abstract: MYH9 disorder is a rare autosomal-dominant disorder. We previously reported that it is caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9 disorder causes congenital macrothrombocytopenia accompanied by progressive sensorineural hearing loss, nephropathy, and cataract. However, there are few reports that describe the audiological features of MYH9 disorder. The objective of this study was to characterize auditory and other phenotypes of patients with MYH9 disorder. We examined nine subjects from one Japanese family. Audiological, ophthalmological, hematological, and imaging examinations were used to assess clinical features. We carried out genetic analysis of the causative gene, MYH9. Five subjects exhibited macrothrombocytopenia and neutrophil cytoplasmic inclusion bodies. Immunofluorescence analysis of neutrophil NMMHC-IIA revealed abnormal type II localization. Two subjects had high-frequency dominant hearing loss, which was adult onset and progressive. Only one subject had cataract. MYH9 sequencing analysis of all thrombocytopenic subjects revealed a heterozygous c.4270G>A mutation in exon 30 (p.D1424N). We identified five patients with MYH9 disorder from the family. The hearing impairment associated with MYH9 disorder in this family was characterized as adult onset, progressive, and high-frequency dominant. Hematological manifestations of MYH9 disorder show complete penetrance, whereas extra-hematological manifestations show incomplete penetrance and variable expressivity in this family.
authors.affiliation: Department of Otolaryngology, Japanese Red Cross Shizuoka Hospital, 8-2 Outemachi, Aoi-ku, Shizuoka, 420-0853, Japan. wasano@a5.keio.jp.|Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo, 152-8902, Japan. wasano@a5.keio.jp.|Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. wasano@a5.keio.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wasano
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo, 152-8902, Japan.|Medical Genetics Center, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo, 152-8902, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, 460-0001, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002386:Cataract / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005455:Fluorescent Antibody Technique; D006316:Hearing Loss, High-Frequency / Q000235:genetics* / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000378:metabolism; D009154:Mutation; D018995:Myosin Heavy Chains / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D013921:Thrombocytopenia / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains
keywords: Cataract; MYH9 disorder; Macrothrombocytopenia; Nephropathy; Sensorineural hearing loss; Variable expressivity