title: Clinical and molecular characteristics in three families with biallelic mutations in IGHMBP2.
abstract: Biallelic mutations in IGHMBP2 cause spinal muscular atrophy with respiratory distress type 1 (SMARD1) or Charcot-Marie-Tooth type 2S (CMT2S). We report three families variably affected by IGHMBP2 mutations. Patient 1, an 8-year-old boy with two homozygous variants: c.2T>C and c.861C>G, was wheelchair bound due to sensorimotor axonal neuropathy and chronic respiratory failure. Patient 2 and his younger sister, Patient 3, had compound heterozygous variants: c.983_987delAAGAA and c.1478C>T. However, clinical phenotypes differed markedly as the elder with sensorimotor axonal neuropathy had still unaffected respiratory function at 4.5 years, whereas the younger presented as infantile spinal muscular atrophy and died from relentless respiratory failure at 11 months. Patient 4, a 6-year-old girl homozygous for IGHMBP2 c.449+1G>T documented to result in two aberrant transcripts, was wheelchair dependent due to axonal polyneuropathy. The clinical presentation in Patients 1 and 3 were consistent with SMARD1, whereas Patients 2 and 4 were in agreement with CMT2S.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Christeen Ramane J
authors.initials: CR
authors.lastname: Pedurupillay
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Silja S
authors.initials: SS
authors.lastname: Amundsen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tuva
authors.initials: T
authors.lastname: Barøy
authors.affiliation: Women and Children's Division, Department of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway; Unit for Congenital and Hereditary Neuromuscular Disorders, Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Magnhild
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Blomhoff
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Barbro Fossøy
authors.initials: BF
authors.lastname: Stadheim
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ørstavik
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Holmgren
authors.affiliation: Molecular Biology laboratory, Department of Zoology, University of Gujrat, Gujrat, Pakistan.
authors.forename: Tahir
authors.initials: T
authors.lastname: Iqbal
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Doriana
authors.initials: D
authors.lastname: Misceo
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Women and Children's Division, Department of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway. Electronic address: petter.stromme@medisin.uio.no.
authors.forename: Petter
authors.initials: P
authors.lastname: Strømme
mesh_terms: D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D012131:Respiratory Insufficiency / Q000235:genetics / Q000378:metabolism; D035781:Siblings; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors
keywords: Axonal polyneuropathy; CMT2S; IGHMBP2; SMARD1; Spinal muscular atrophy