title: Two Japanese Patients With SMA Type 1 Suggest that Axonal-SMN May Not Modify the Disease Severity.
abstract: BACKGROUND
  Spinal muscular atrophy is caused by survival motor neuron gene SMN1 mutations. SMN1 produces a full-length SMN1 protein isoform encoded by exons 1-7, and an axonal-SMN protein isoform encoded by exons 1-3 and intron 3. The axonal-SMN protein is expressed only in the embryonic period and plays a significant role in axonal growth. However, there has been no report on contribution of axonal-SMN to spinal muscular atrophy severity until now.
  
  
  METHODS
  Two Japanese boys with spinal muscular atrophy type 1 in our study presented with generalized muscle weakness and respiratory insufficiency soon after birth and required an artificial ventilator from early infancy. Patient 1 was compound heterozygous for two SMN1 mutations, whole-gene deletion, and an intragenic mutation (c.819_820insT). He retained one copy of SMN1 producing the N-terminal part of SMN1 including axonal-SMN. On the other hand, patient 2 was homozygous for SMN1 deletion. Both of them showed the same copy number of spinal muscular atrophy-modifying genes, NAIP and SMN2. These findings suggested that the C-terminal domain of full-length SMN1 determined the severity, irrespective of presence or absence of axonal-SMN expression.
  
  
  CONCLUSIONS
  In patient 1, the C-terminal domain of full-length SMN1 determined spinal muscular atrophy severity, rather than the axonal-SMN, one copy of which could be present and intact. The presence or absence of axonal-SMN may not impact disease severity in spinal muscular atrophy type 1 patients.
authors.affiliation: Department of Pediatrics, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Hyogo, Japan; Department of Pediatrics, Toyooka Public Hospital, Toyooka, Hyogo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Hyogo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Pediatrics, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Hyogo, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Maihara
authors.affiliation: Department of Community Medicine and Social Health Care, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Nihayatus
authors.initials: N
authors.lastname: Sa'adah
authors.affiliation: Department of Community Medicine and Social Health Care, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Nur Imma Fatimah
authors.initials: NI
authors.lastname: Harahap
authors.affiliation: Department of Community Medicine and Social Health Care, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Dian Kesumapramudya
authors.initials: DK
authors.lastname: Nurputra
authors.affiliation: Department of Community Medicine and Social Health Care, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Mawaddah
authors.initials: M
authors.lastname: Ar Rochmah
authors.affiliation: Department of Community Medicine and Social Health Care, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishimura
authors.affiliation: Division of Child Neurology, Department of Neurology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Saito
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Community Medicine and Social Health Care, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: nishio@med.kobe-u.ac.jp.
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
mesh_terms: D001369:Axons / Q000378:metabolism*; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D014897:Spinal Muscular Atrophies of Childhood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein
keywords: C-terminal domain; axonal-SMN; full-length SMN1; spinal muscular atrophy