title: Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions.
abstract: The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS), and Fechtner syndrome (FTNS), are rare platelet disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like leukocyte inclusions. The locus for these disorders was previously mapped on chromosome 22q12.3-q13.2 and the disease gene was recently identified as MYH9, the gene encoding the nonmuscle myosin heavy chain-A. To elucidate the spectrum of MYH9 mutations responsible for the disorders and to investigate genotypephenotype correlation, we examined MYH9 mutations in an additional 11 families and 3 sporadic patients with the disorders from Japan. Korea, and China. All 14 patients had heterozygous MYH9 mutations, including three known mutations and six novel mutations (three missense and three deletion mutations). Two cases had Alport manifestations including deafness, nephritis, and cataracts and had R1165C and E1841K mutations, respectively. However, taken together with three previous reports, including ours, the data do not show clear phenotype-genotype relationships. Thus, MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kunishima
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: N
authors.initials: N
authors.lastname: Amemiya
authors.forename: Y M
authors.initials: YM
authors.lastname: Choi
authors.forename: N
authors.initials: N
authors.lastname: Hosaka
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Jung
authors.forename: S
authors.initials: S
authors.lastname: Mamiya
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Miyajima
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Ruan
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: K S
authors.initials: KS
authors.lastname: Song
authors.forename: H J
authors.initials: HJ
authors.lastname: Yoon
authors.forename: T
authors.initials: T
authors.lastname: Kamiya
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D001208:Asia; D001483:Base Sequence; D001792:Blood Platelets / Q000473:pathology*; D017931:DNA Primers / Q000235:genetics; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D007962:Leukocytes / Q000473:pathology*; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D009394:Nephritis, Hereditary / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D013921:Thrombocytopenia / Q000097:blood* / Q000235:genetics*
chemical_list: D017931:DNA Primers; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains