title: Clinical diversity caused by novel IGHMBP2 variants.
abstract: Immunoglobulin helicase μ-binding protein 2 (IGHMBP2) gene is responsible for Charcot-Marie-Tooth disease (CMT) type 2S and spinal muscular atrophy with respiratory distress type 1 (SMARD1). From June 2014 to December 2015, we collected 408 cases, who referred to our genetic laboratory for genetic analysis, suspected with CMT disease or other inherited peripheral neuropathies (IPNs) on the basis of clinical manifestations and electrophysiological studies. Mutation screening was performed using Ion AmpliSeq Custom Panels, which comprise 72 disease-causing or candidate genes of IPNs. We identified novel homozygous or compound heterozygous variants of IGHMBP2 in four patients. Three patients presented with childhood-onset axonal predominant sensorimotor polyneuropathies, whereas the other case was diagnosed with SMARD1, manifesting as low birth weight, weak cry, reduced spontaneous movement and developed respiratory distress 4 months after birth. We present the original report of CMT type 2S in Japan, and illustrate that recessive IGHMBP2 variants account for ~1.6% of axonal CMT in our cohort.
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Yuan
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hashiguchi
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Department of Neurology, The Jikei University Kashiwa Hospital, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yaguchi
authors.affiliation: Department of Neurology, Kansai Electric Power Hospital, Osaka, Japan.
authors.forename: Koji
authors.identifier: http://orcid.org/0000-0002-5364-2280
authors.initials: K
authors.lastname: Tsuzaki
authors.affiliation: Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wada-Isoe
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hiramatsu
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors