Pelizaeus-Merzbacher disease: genes and variants

Genes linked to Pelizaeus-Merzbacher disease

• PLP1: Myelin proteolipid protein

  It supports central-nervous-system myelin structure and is required for oligodendrocyte and axonal integrity. Gene duplication most commonly causes Pelizaeus-Merzbacher disease, while other variants can cause spastic paraplegia type 2 or milder leukodystrophy.

  51 disease-causing and 26 uncertain variants in PLP1 are linked to Pelizaeus-Merzbacher disease.

Where Pelizaeus-Merzbacher disease variants cluster

• PLP1 Transmembrane (positions 234–260): 9 of 51 disease-causing changes, 1.8× more than its size predicts.

Known disease-causing variants in Pelizaeus-Merzbacher disease

Same protein, different disease

• Hereditary spastic paraplegia is also caused by PLP1 variants; they fall partly in the same places as the Pelizaeus-Merzbacher disease variants (14 disease-causing).

Diseases related to Pelizaeus-Merzbacher disease

• Hereditary spastic paraplegia, also linked to PLP1
• Auditory neuropathy spectrum disorder, also linked to PLP1

Frequently asked questions

Which genes are linked to Pelizaeus-Merzbacher disease?

In CATVariant, Pelizaeus-Merzbacher disease is linked to 1 analyzed protein: PLP1 (Myelin proteolipid protein).

How many genetic variants are linked to Pelizaeus-Merzbacher disease?

77 variants: 51 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 26 are of uncertain significance or have conflicting reports.

Which uncertain variants in Pelizaeus-Merzbacher disease look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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