title: GNE myopathy associated with congenital thrombocytopenia: a report of two siblings.
abstract: GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congenital thrombocytopenia who harbored two compound heterozygous GNE mutations, p.V603L and p.G739S. Thrombocytopenia, which is characterized by shortened platelet lifetime rather than ineffective thrombopoiesis, has been observed since infancy. We performed exome sequencing and array CGH to identify the underlying genetic etiology of thrombocytopenia. No pathogenic variants were detected among the known causative genes of recessively inherited thrombocytopenia; yet, candidate variants in two genes that followed an autosomal recessive mode of inheritance, including previously identified GNE mutations, were detected. Alternatively, it is possible that the decreased activity of GNE/MNK itself, which would lead to decreased sialic content in platelets, is associated with thrombocytopenia in these patients. Further investigations are required to clarify the association between GNE myopathy and the pathogenesis of thrombocytopenia.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan; Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Izumi
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Rikiishi
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan; Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Endo
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Warita
authors.affiliation: Department of Neurology and Division of Clinical Research, Sendai Nishitaga National Hospital, Sendai, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Konno
authors.affiliation: Department of Neurology and Division of Clinical Research, Sendai Nishitaga National Hospital, Sendai, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tateyama
authors.affiliation: Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan. Electronic address: aokim@med.tohoku.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D035781:Siblings; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
keywords: Distal myopathy with rimmed vacuoles; Exome sequencing; GNE; Sialic acid; Thrombocytopenia; UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase