Severe microcephaly

Gene: PLAA

Red List (low evidence)

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

1 review

Rebecca Foulger (Genomics England curator)

Comment on list classification: Added PLAA to panel based on progressive microcephaly phenotypes recorded in 2 papers (PMID:28007986 and PMID:28413018) and association with MIM:617527. However microcephaly was not consistently reported at birth, and based on current reports the phenotype isn't severe enough to be considered as a green gene for this panel.
28 Aug 2017, 9:42 a.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. Microcephaly developed in the first year- OFC of affected individuals varies between - and -4 at birth, and progresses to -3 to -6 after 1 year (Figure 1F). Microcephaly also seen in mouse model.
28 Aug 2017, 9:40 a.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. Head circumference was normal at birth and decreased to >2 SD below mean in the ensuing years. In 2 patients, they observed an unexplained gradual increase in head circumference up to 75% after the age of 5 years.
28 Aug 2017, 9:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Other
Phenotypes
  • Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527
OMIM
603873
Clinvar variants
Variants in PLAA
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Aug 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

28 Aug 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PLAA were set to 28007986; 28413018

28 Aug 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

PLAA was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other

28 Aug 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

PLAA was created by rfoulger