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Genetic epilepsy syndromes

Gene: PLAA

Green List (high evidence)

PLAA (phospholipase A2 activating protein)
EnsemblGeneIds (GRCh38): ENSG00000137055
EnsemblGeneIds (GRCh37): ENSG00000137055
OMIM: 603873, Gene2Phenotype
PLAA is in 5 panels

4 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR neurodegenerative disorder with progressive microcephaly, spasticity and brain abnormalities, seizures are a variable feature of this disorder. Falik Zaccai et al,2017 - large consang Israeli family and a similarly aff patient from an unrelated consang family from the same geographical region - 3/7 had seizures - all had the same hom missense variant and haplotype analysis confirmed a common ancestral haplotype. Functional studies done. Hall et al, 2017 - 10 patients from 4 consang families of Pakistani or Saudi origin - 8/10 developed seizures 3 families had a hom missense variant and the other had a hom fs variant.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with progressive microcephaly spasticity and brain anomalies, 617527

Publications

Eleanor Williams (Genomics England Curator)

Comment when marking as ready: Sufficient cases for disease association, >3 cases with seizures
Created: 22 Nov 2018, 2:01 p.m.
Comment on list classification: 3 variants found in 5 families (but two families likely to have common ancestral haplotype). Seizures reported in all families.
Created: 22 Nov 2018, 1:55 p.m.
PLAA is associated with Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies in OMIM and Lethal Infantile Epileptic Encephalopathy in Gene2Phenotype (probable).

Falik Zaccai et al. (2017)(PMID: 28007986) report 2 consanguineous families from Israel. In both, patients have a p.Leu752Phe homozygous variant that segregates with the family. Haplotype analysis (supported a common ancestral haplotype in Families A and B. Functional studies using patient fibroblasts indicate a loss of function effect for the variant. Some affected individuals in both families show seizures.

Hall et al. (2017)(PMID: 28413018) report 4 unrelated families. In 3 (all originally from Pakistan) a homozygous p.Gly23Val change was found, in the other family (Middle Eastern) a p.Leu24Profs*55 change. In all 4 families individuals presented with seizures. Functional studies show that PLAA is essential for neural function.

Summary, 3 variants found with functional evidence that the are deleterious. >3 cases of seizures.
Created: 22 Nov 2018, 1:46 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seizures are part of the phenotype in this neurodevelopment disorder.
Created: 19 Aug 2018, 11:15 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM#617527

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies 617527
  • Lethal Infantile Epileptic Encephalopathy
OMIM
603873
Clinvar variants
Variants in PLAA
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to PLAA.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to PLAA.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are part of the pheno

22 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

22 Nov 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PLAA were changed from to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies 617527; Lethal Infantile Epileptic Encephalopathy

22 Nov 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PLAA were set to

22 Nov 2018, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: PLAA was changed from to BIALLELIC, autosomal or pseudoautosomal

22 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to PLAA. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

PLAA was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

PLAA was created by Sarah Leigh