ClinGen Dosage Sensitivity Curation Page

PLP1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)

Haploinsufficiency phenotype comments:

Loss of function mutations, including whole gene deletions, are associated with PLP1-related disorders, including Pelizaeus-Merzbacher disease and spastic-paraplegia 2. Whole gene deletions account for 2% of individuals with Pelizaeus-Merzbacher disease. Some females with clinical symptoms have been reported, most commonly with mild mutations and random X-inactivation. See GeneReviews.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity phenotype comment:

Whole gene duplications account for about 50% of patients with PLP1-related disorders, including Pelizaeus-Merzbacher disease and spastic-paraplegia 2. Duplications are typically tandem, but can also be insertional. Triplications and quintuplications have also been observed. Female carriers of duplications are less likely to have clinical manifestations and more likely to have favorably skewed X-inactivation. See GeneReviews.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.