title: Clinical and genetic characterization of a 2-year-old boy with complete PLP1 deletion.
abstract: We report herein a case of 2-year-old boy diagnosed with a mild form of Pelizaeus-Merzbacher disease due to deletion of the entire proteolipid protein 1 (PLP1) gene. The patient demonstrated spastic quadriplegia, mental retardation, and microcephaly. He exhibited brainstem auditory evoked potentials with prolonged interpeak latencies and magnetic resonance imaging characteristics suggestive of hypomyelination in most areas of the brain with the exception of the brainstem, cerebellar peduncles, corpus callosum, and the posterior limbs of the internal capsules. Proton magnetic resonance spectroscopy revealed a mildly reduced ratio of N-acetyl aspartate to creatine levels in the white matter, suggesting axonal involvement. Additionally, nerve conduction velocity of the lower extremities was mildly decreased. Genetic analysis showed a deletion of PLP1 in this patient. Further genome mapping followed by sequence analysis of the deletion breakpoints revealed that a genomic region, about 73 kb in length, including the entire PLP1 and RAB9B, was deleted. The size of the deletion was the smallest among those previously reported in this region. Except for the 1-base pair microhomology, there were no homologous sequences between the regions around the distal and proximal breakpoints, which suggests that the deletion occurred by nonhomologous end joining.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. htorys@pediatr.med.kyushu-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Torisu
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwaki
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takeshita
authors.forename: Akio
authors.initials: A
authors.lastname: Hiwatashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sanefuji
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fukumaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D002675:Child, Preschool; D002874:Chromosome Mapping / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D017353:Gene Deletion; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017354:Point Mutation
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human