Hereditary Spastic Paraplegia - paediatric

Gene: PNPLA8

Green List (high evidence)

PNPLA8 (patatin like phospholipase domain containing 8)
EnsemblGeneIds (GRCh38): ENSG00000135241
EnsemblGeneIds (GRCh37): ENSG00000135241
OMIM: 612123, Gene2Phenotype
PNPLA8 is in 8 panels

1 review

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 15/23 individuals (info available) had spasticity (onset in early childhood).

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Created: 5 Sep 2024, 1:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
PNPLA8-related neurological diseases

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
OMIM
612123
Clinvar variants
Variants in PNPLA8
Penetrance
None
Publications
Panels with this gene

History Filter Activity

5 Sep 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pnpla8 has been classified as Green List (High Evidence).

5 Sep 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related

5 Sep 2024, Gel status: 3

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: pnpla8 has been classified as Green List (High Evidence).

5 Sep 2024, Gel status: 1

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

Chirag Patel (Genetic Health Queensland)

gene: PNPLA8 was added gene: PNPLA8 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPLA8 were set to PMID: 39082157 Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases Review for gene: PNPLA8 was set to GREEN gene: PNPLA8 was marked as current diagnostic