Hereditary spastic paraplegia

Gene: PCYT2

Green List (high evidence)

PCYT2 (phosphate cytidylyltransferase 2, ethanolamine)
EnsemblGeneIds (GRCh38): ENSG00000185813
EnsemblGeneIds (GRCh37): ENSG00000185813
OMIM: 602679, Gene2Phenotype
PCYT2 is in 4 panels

1 review

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: New gene for HSP. There are more than 3 unrelated cases to support the HSP phenotype caused by homozygous mutation in the gene encoding phosphoethanolamine cytidylyltransferase
Created: 29 Oct 2019, 12:01 p.m. | Last Modified: 29 Oct 2019, 12:01 p.m.
Panel Version: 1.207
New publication (2019) : Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia: Vaz, Frédéric M, PMID: 31637422. Identified five individuals with biallelic PCYT2 variants clinically characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy.

CTP:phosphoethanolamine cytidylyltransferase (ET) is encoded by the PCYT2 gene. Using patient fibroblasts they demonstrated that the variants were hypomorphic, resulting in altered but residual ET protein levels and concomitant reduced enzyme activity without affecting mRNA levels. The significantly better survival of hypomorphic CRISPR- Cas9 generated pcyt2 zebrafish knockout compared to a complete knockout, in conjunction with previously described data on the Pcyt2 mouse model, indicates that complete loss of ET function may be incompatible with life in vertebrates. Lipidomic analysis revealed profound lipid abnormalities in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency.

The data establishes that PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirmed that etherlipid homeostasis is important for the development and function of the brain.
Sources: Literature
Created: 29 Oct 2019, 11:53 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Complex hereditary spastic paraplegia



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Green
  • Literature
  • Complex hereditary spastic paraplegia
Clinvar variants
Variants in PCYT2
Panels with this gene

History Filter Activity

29 Oct 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: pcyt2 has been classified as Green List (High Evidence).

29 Oct 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Louise Daugherty (Genomics England Curator)

gene: PCYT2 was added gene: PCYT2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to Complex hereditary spastic paraplegia Review for gene: PCYT2 was set to GREEN