title: A novel PLP1 frameshift mutation causing a milder form of Pelizaeus-Merzbacher disease.
abstract: BACKGROUND
  Pelizaeus-Merzbacher disease (PMD), a hypomyelinating leukodystrophy, and the related but less severe allelic spastic paraplegia 2 (SPG2) are caused by mutations in the proteolipid protein 1 (PLP1) gene. Magnetic resonance imaging (MRI) is pivotal for diagnosing these disorders. The severity of PMD/SPG2 varies, and for a milder form of PMD, there have been some reports of near-normal findings in T1-weighted images but abnormal findings in T2-weighted images.
  
  
  METHODS
  We report the case of a 5-year-old boy diagnosed with a milder form of PMD caused by a novel PLP1 mutation in exon 3: c.300delC (p.I100IfsX13). He had delayed development from several months of age and was able to walk with support at 19 months in spite of the spasticity in his lower extremities. Hypomyelination was noted at 12 months by brain MRI. Motor nerve conduction studies showed decreased velocities with reduced amplitudes. Follow-up MRI at 1-year intervals from 18 months until 55 months of age showed gradual myelination progress.
  
  
  CONCLUSIONS
  The single nucleotide deletion identified in this patient can cause a frameshift and premature termination of PLP1. Via the nonsense-mediated mRNA decay mechanism of this mutation will result in loss-of-function, leading to a milder form of PMD. The present case is compatible with previously reported cases of milder form of PMD. We incidentally identified progressive myelination in this patient by T1-weighted images obtained by serial MRI. This finding adds to our understanding of the pathological stages of a milder form of PMD.
authors.affiliation: Department of Neurology, Gunma Children's Medical Center, Gunma 377-8577, Japan. Electronic address: shiihara-ind@umin.net.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiihara
authors.affiliation: Department of Neurology, Gunma Children's Medical Center, Gunma 377-8577, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Gunma Children's Medical Center, Gunma 377-8577, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Uematsu
authors.affiliation: Division of Medical Genetics, Gunma Children's Medical Center, Gunma 377-8577, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Sameshima
mesh_terms: D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D016057:Evoked Potentials, Auditory, Brain Stem; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: Magnetic resonance imaging; Myelination; Nonsense-mediated decay; Pelizaeus–Merzbacher disease; Proteolipid protein; Spastic paraplegia 2; mRNA