See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as multiplex ligation-dependent probe amplification (MLPA), a gene-targeted microarray, quantitative PCR, and long-range PCR designed to detect single-exon deletions or duplications.

The majority of gene dosage changes are tandem duplications occurring in Xq22, which include all of PLP1. In rare instances, the duplicated region can be inserted at some distance from Xq22; four insertions have been reported: at Xp22, Xq28 [Woodward et al 1998, Hodes et al 2000], and 19qtel [Inoue et al 2002]; and in the Y chromosome [Woodward et al 2005]. Triplication, partial triplication, and quintuplication of PLP1 also occur [Boespflug-Tanguy et al 1994, Woodward et al 1998, Wolf et al 2005, Combes et al 2006]. In simplex females, PLP1 duplication often occurs with complex chromosomal rearrangements.

Whole-gene deletions of PLP1 occur in fewer than 2% of those with the Pelizaeus-Merzbacher disease phenotype [Raskind et al 1991; Boespflug-Tanguy et al 1994; Inoue et al 2002; Shaffer, unpublished observations]. Inoue et al [2002] determined that the individual originally described with a PLP1 deletion has a complex rearrangement with both a deletion of PLP1 and an inverted insertion of a more distal portion of the X chromosome at the deletion junction. In addition, this individual has duplication of a region distal of PLP1 [Hobson et al 2002, Lee et al 2007]. Partial PLP1 deletion has also been reported [Combes et al 2006].

Depending on the method used, larger deletion or duplication events may be detected. Position effect of a duplication identified by FISH that was near but did not include PLP1 has been invoked as the cause of the neurologic syndrome in a man with spastic paraplegia [Lee et al 2006].

Sequence analysis which should include analysis of intron 3B detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

An inversion of the X chromosome with a breakpoint 70 kbp upstream of PLP1, identified by chromosome analysis, was proposed to disrupt PLP1 expression through position effect in a child with PMD-like syndrome [Muncke et al 2004].