title: A splicing mutation of proteolipid protein 1 in Pelizaeus-Merzbacher disease.
abstract: A patient with an unusually mild form of Pelizaeus-Merzbacher disease was studied. Clinically, mild developmental delay with acquisition of assisted walking at 16months and mild spastic tetraplegia were evident, but no nystagmus, cerebellar, or extra-pyramidal signs were present. PLP1 mutation analysis revealed a nucleotide substitution adjacent to the acceptor site of intron 3, NM_000533.4:c.454-9T>G. Expression analysis using the patient's leukocytes demonstrated an additional abnormal transcript including the last 118bp of intron 3. In silico prediction analysis suggested the reduction of wild-type acceptor activity, which presumably evokes the cryptic splicing variant. Putative cryptic transcript results in premature termination, which may explain the mild clinical phenotype observed in this patient.
authors.affiliation: Division of Child Neurology, Chiba Children's Hospital, Chiba, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Omata
authors.affiliation: Laboratory Medicine, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nagai
authors.affiliation: Division of Neurology, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimbo
authors.affiliation: Division of Neurology, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan; Division of Genetics, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-0815, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Koizume
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-0815, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Division of Genetics, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.affiliation: Division of Neurology, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan.
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Division of Neurology, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama 232-855, Japan; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-0815, Japan; Department of Pediatrics, Jichi Medical School, Shimono, Japan. Electronic address: hosaka@jichi.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D007438:Introns; D007962:Leukocytes / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics* / Q000378:metabolism; D020371:Pelizaeus-Merzbacher Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: DM20; Hypomyelinating leukodystrophy; Intronic mutation; PLP1