J Korean Med Sci.  2008 Apr;23(2):328-331. 10.3346/jkms.2008.23.2.328.

Identification of Proteolipid Protein 1 Gene Duplication by Multiplex Ligation-Dependent Probe Amplification: First Report of Genetically Confirmed Family of Pelizaeus-Merzbacher Disease in Korea

• Kim SJ
• Yoon JS
• Baek HJ
• Suh SI
• Bae SY
• Cho HJ
• Ki CS

• KMID: 1713470
• DOI: http://doi.org/10.3346/jkms.2008.23.2.328

Abstract

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with a prototype of a dysmyelinating leukodystrophy that is caused by a mutation in the proteolipid protein 1 (PLP1) gene on the long arm of the X chromosome in band Xq22. This mutation results in abnormal expression or production of PLP. We here present a Korean boy with spastic quadriplegia, horizontal nystagmus, saccadic gaze, intentional tremor, head titubation, ataxia, and developmental delay. The brain magnetic resonance imaging (MRI) showed abnormally high signal intensities in the white matter tract, including a subcortical U fiber on the T2-weighted and fluid attenuated inversion recovery (FLAIR) image. The chromosomal analysis was normal; however, duplication of the PLP1 gene in chromosome Xq22 was detected when the multiplex ligation-dependent probe amplification (MLPA) method was used. We also investigated the pedigree for a genetic study related to PMD. This case suggests that the duplication mutation of the PLP1 gene in patients with PMD results in a mild clinical form of the disorder that mimics the spastic quadriplegia of cerebral palsy.

Keyword

Gene Amplification; Pelizaeus-Merzbacher Disease; Quadriplegia; Propeolipid Protein Duplication

MeSH Terms

Brain/*pathology
Child, Preschool
Chromosome Mapping
Chromosomes, Human, X
Developmental Disabilities/diagnosis/genetics
Exons
Gene Duplication
Humans
Korea
Magnetic Resonance Imaging/methods
Mutation
Myelin Proteolipid Protein/genetics
Myelin Sheath/chemistry
Pelizaeus-Merzbacher Disease/*diagnosis/*genetics
Polymerase Chain Reaction/*methods

Figure

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  Fig. 1 Axial T2-weighted (A) and FLAIR (B) brain MRI scans at the level of the centrum semiovale in a 52-month-old boy with PMD. Extensive high signal intensity in white matter including subcortical U fiber is seen. Note the residual myelinated fibers (arrows), showing isosignal intensity and giving the "tigroid" appearance sometimes presented in PMD, within the diffuse demyelinating white matter.

• 

  Fig. 2 Multiplex ligation-dependent probe amplification (MLPA) results. (A) Electropherograms after MLPA analysis of the family. All peaks corresponding to the 7 exons of the PLP1 gene in the proband and his brother are higher than peaks in the proband's father but similar to peaks in female control due to PLP1 gene duplication. The proband's mother has even higher peaks than female control. (B) The relative copy numbers for each PLP1 exon were shown.

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