Intellectual disability
Gene: PLXNA1

PLXNA1 (plexin A1)
EnsemblGeneIds (GRCh38): ENSG00000114554
EnsemblGeneIds (GRCh37): ENSG00000114554
OMIM: 601055, Gene2Phenotype
PLXNA1 is in 4 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.

Panel Version: 5.286

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 11 Oct 2023, 9:34 a.m.
Last Modified: 11 Oct 2023, 9:34 a.m.
Panel version: 5.286

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for this gene to be promoted to GREEN at the next major review. The MOI can also be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are more than three cases each with both monoallelic and biallelic variants.
Created: 2 May 2023, 3:19 p.m. | Last Modified: 2 May 2023, 3:19 p.m.

Panel Version: 5.80

Monoallelic cases:

PMID:28464511 reported a male patient with a de novo variant in PLXNA1 and presenting with intractable infantile onset epilepsy, and intellectual disability with autism spectrum disorder. In addition, this patient also had features suggestive of Dubowitz syndrome, including growth failure, dermatologic symptoms, and characteristic dysmorphic facial features.

PMID:34054129 reported ten cases from seven families with PLXNA1 variants. Of these cases, three unrelated cases had monoallelic de novo variants and presented with global developmental delay, seizures and craniofacial, brain and eye anomalies.

PMID:34415653 reported a 38-year-old patient with developmental delay who developed parkinsonism later in life. A heterozygous PLXNA1 variant was identified in this patient.

Biallelic cases:

Out of ten cases reported in PMID:34054129, seven cases from four unrelated families exhibited biallelic variants in PLXNA1 gene (two families each with homozygous and compound heterozygous variants). They presented with global developmental delay and craniofacial, brain and eye anomalies. However, seizures are not reported in biallelic cases except one family (15 episodes of febrile and nonfebrile seizures reported in family A).

The biallelic variants in this gene has been associated with phenotypes in OMIM (MIM #619955). However, both monoalellic and biallelic variants in this gene has been associated with phenotypes in Gene2Phenotype (with 'limited' rating).

Functional studies:

Structural modeling of missense variants in PLXNA1 suggests distortion in the native protein. Knockdown of plxna1a leads to cerebral anomalies and eye anomalies in zebrafish larvae.
Created: 2 May 2023, 3:12 p.m. | Last Modified: 2 May 2023, 3:12 p.m.

Panel Version: 5.75

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062

Publications

Created: 2 May 2023, 3:12 p.m.
Last Modified: 2 May 2023, 3:12 p.m.
Panel version: 5.75

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Dworschak et al. (2021) via WES reported 10 patients from 7 families with biallelic (n=7) or de novo (n=3) PLXNA1 variants. Shared phenotypic features include global developmental delay (9/10), brain anomalies (6/10), and eye anomalies (7/10). Seizures were predominantly reported in patients with monoallelic variants. Zebrafish studies showed an embryonic role of plxna1a in the development of the central nervous system and the eye. Biallelic variants in the extracellular Plexin-A1 domains lead to impaired dimerization or lack of receptor molecules, whereas monoallelic variants in the intracellular Plexin-A1 domains might impair downstream signaling through a dominant-negative effect.
Sources: Literature
Created: 11 Oct 2021, 9:55 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with cerebral and eye anomalies

Publications

34054129

Created: 11 Oct 2021, 9:55 a.m.

Panel version: 3.1338

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955
developmental and epileptic encephalopathy, MONDO:0100062

OMIM

601055

Clinvar variants

Variants in PLXNA1

Penetrance

None

Publications

Panels with this gene

History Filter Activity

11 Oct 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_23_promote_green was removed from gene: PLXNA1.

11 Oct 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to PLXNA1. Source Expert Review Green was added to PLXNA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

2 May 2023, Gel status: 2