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Intellectual disability

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

Helen Brittain (Genomics England Curator)

Comment when marking as ready: Appropriate phenotype, sufficient cases
Created: 13 Nov 2017, 4:10 p.m.

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Amber to Green: Although not yet curated in DD-G2P, 3 cases in different populations from 2 different papers (PMID:28007986 and PMID:28413018) support causation of an ID phenotype (2 families plus 1 individual).
Created: 17 Aug 2017, 12:38 p.m.
In 7 infants from 3 consanguineous Pakistani families with a lethal form of NDMSBA, Hall et al. (2017, PMID:28413018) identified a homozygous missense mutation in the PLAA gene (G23V). Haplotype analysis indicated a common founder rather than a recurrent mutation. Hall et al., also report a Saudi Arabian patient with NDMSBA and homozygosity for a 1-bp duplication in the PLAA gene resulting in a frameshift and premature termination. All 4 patients had profound developmental delay and seizures.
Created: 17 Aug 2017, 12:34 p.m.
In 7 patients from 2 consanguineous Israeli families with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA, MIM:617527), Falik Zaccai et al. (2017, PMID:28007986) identified a homozygous missense mutation in the PLAA gene (L752F). The variant was found in a heterozygous state in 3 of 92 residents from the local village. Haplotype analysis indicated a common ancestral haplotype in the 2 families. All patients had severe mental and language developmental delay.
Created: 17 Aug 2017, 12:33 p.m.
Comment on phenotypes: Phenotypes of MIM:617527 include global developmental delay, mental retardation and progressive microcephaly (recorded in both PMID:28007986 and PMID:28413018).
Created: 17 Aug 2017, 12:27 p.m.

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_manual . Main mutation mechanism : Missense and Loss of function
Created: 27 Jul 2017, 8:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

  • Manual assessment of Genes of interest from literature searches and personal communication

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Promoted to Green from Amber more than three unrelated cases. This is a neurodevelopmental disorder characterized by infantile onset of progressive microcephaly, spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy.
Created: 29 Nov 2017, 2:10 p.m.
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.
Created: 28 Jul 2017, 3:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527; NDMSBA; Epileptic Encephalopathy

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
Phenotypes
  • Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527
  • NDMSBA
  • Epileptic Encephalopathy
OMIM
603873
Clinvar variants
Variants in PLAA
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to PLAA.

12 Mar 2018, Gel status: 4

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene PLAA was set to ['28413018', '28007986']

17 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

17 Aug 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PLAA were set to 28007986; 28413018

17 Aug 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for PLAA were set to Epileptic Encephalopathy; Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527

28 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

27 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

PLAA was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene

27 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

PLAA was created by BRIDGE