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Intellectual disability

Gene: PRRT2

Amber List (moderate evidence)
PRRT2 (proline rich transmembrane protein 2)
EnsemblGeneIds (GRCh38): ENSG00000167371
EnsemblGeneIds (GRCh37): ENSG00000167371
OMIM: 614386, Gene2Phenotype
PRRT2 is in 13 panels

7 reviews

Arina Puzriakova (Genomics England Curator)

New publication identified by Dmitrijs Rots (PMID: 36180924) highlights an individual with a 'severe neurodevelopmental disorder' and a c.649dup (p.R217fs*8) variant in the PRRT2 gene in trans with the recurrent 16p11.2 BP4-BP5 deletion. 16p11.2 haploinsufficiency itself is known to be associated with ID (ISCA-37400-Loss) and therefore it is difficult to ascertain the contribution of the PRRT2 variant to the patients phenotype. This should be considered if further cases arise, but leaving this gene as Amber for now.
Created: 27 Feb 2023, 2:38 p.m. | Last Modified: 27 Feb 2023, 2:38 p.m.
Panel Version: 4.79
Created: 27 Feb 2023, 2:38 p.m.
Last Modified: 27 Feb 2023, 2:38 p.m.
Panel version: 4.79

Dmitrijs Rots (Children's Clinical University Hospital)

I don't know

New case with ID and biallelic variant reported in 36180924.
Created: 8 Oct 2022, 11:04 p.m. | Last Modified: 8 Oct 2022, 11:04 p.m.
Panel Version: 3.1737

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 8 Oct 2022, 11:04 p.m.
Last Modified: 8 Oct 2022, 11:04 p.m.
Panel version: 3.1737

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: Changed from Green to Amber, as there is not enough evidence in the literature to rate this gene as Green. Rated as Amber as biallelic variants do cause ID but there is not enough evidence to promote further.
Created: 7 Aug 2018, 3:36 p.m.
added watch list tag
Created: 7 Aug 2018, 3:30 p.m.
Internal clinical team notes that it is the biallelic variants of PRRT2 that leads to more significant phenotypes that includes ID. In the literature there are a number of cases for monoallelic variants, the majority of people have seizures ( this gene is green on our Genetic Epilepsy Syndromes panel), and the minority of which have some intellectual component but seems to be mild, so is not in the scope of the ID panel. It is also not clear on whether the ID is secondary to the seizure phenotype in some cases. For biallelic variants, there are only 2 cases currently reported with more a more significant ID phenotype.
Created: 7 Aug 2018, 3:29 p.m.
Comment on phenotypes: changed phenotypes as we are only interested in those associated to biallelic variants of this gene due to association to ID
Created: 27 Jul 2018, 12:04 p.m.
Comment on mode of inheritance: changed to Biallelic as we are only interested in biallelic variants of this gene due to association to ID
Created: 27 Jul 2018, 12:02 p.m.
From Red review from external reviwer this gene was reaccessed. I think there is some general confusion as we have annotated this gene to the wrong phenotype BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME (AD) and not AUTOSOMAL RECESSIVE MENTAL RETARDATION (AR), so is probably why Zornitza Stark rated this gene as Red. I have now added the publications PMID:23352743, 23398397, 21937992 to support ID and suggested MOI is changed and the phenotypes are amended. Past onto internal clinical team for further review and consideration to confirm keeping gene rated as Green or Amber
Created: 26 Jul 2018, 1:30 p.m.
biallelic phenotype includes ID
Created: 26 Jul 2018, 1:16 p.m.
phenotypes associated to biallelic phenotype with includes ID
Created: 26 Jul 2018, 1:16 p.m.
Comment on publications: added publications to support the ID phenotype
Created: 26 Jul 2018, 1:14 p.m.
From Liu YT et al. (2016) PMID: 27172900 Mutations in the proline-rich transmembrane protein 2 gene (PRRT2, NM_145239.2) have been identified to be the causes of many neurological diseases. Heterozygous PRRT2 mutations cause paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), infantile convulsions and choreoathetosis (ICCA), hemiplegic migraine (HM), episodic ataxia (EA), paroxysmal torticollis, or a combination of them ( Although rarely identified, patients with biallelic or homozygous PRRT2 mutations presented complex forms of PKD in combination with intellectual disability or cerebellar atrophy (PMID: 23352743, 25595153, 23398397).
Created: 26 Jul 2018, 1:12 p.m.
G2P lists AUTOSOMAL RECESSIVE MENTAL RETARDATION phenotype, confirmed biallelic loss of function, the evidence listed is a deep sequencing publication Najmabadi et al (20111) PMID:21937992
Created: 26 Jul 2018, 12:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy; mental retardation; movement disorders; paroxysmal disorder, AUTOSOMAL RECESSIVE MENTAL RETARDATION

Created: 26 Jul 2018, 12:41 p.m.

Panel version: 2.297

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Not convinced intellectual disability is part of the phenotype
Created: 20 Jun 2018, 3:19 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 20 Jun 2018, 3:19 p.m.

Panel version: 2.104

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

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_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_omim_20150205_epilepsies;in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 8:09 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; omim_20150205_epilepsies; manju_list; UKGTN_v12; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:12 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

  • 25529582
  • omim.org
  • Personal communication with NIHRBRRD BRIDGE SPEED
  • Version 12 ukgtn.nhs.uk

Created: 2 Aug 2017, 9:53 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:42 a.m.

Panel version: 0.306

History Filter Activity

27 Feb 2023, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439

7 Aug 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: prrt2 has been classified as Amber List (Moderate Evidence).

27 Jul 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439

27 Jul 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PRRT2 were set to Epilepsy; mental retardation; movement disorders; paroxysmal disorder; Autosomal recessive mental retardation

27 Jul 2018, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: PRRT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

27 Jul 2018, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: PRRT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

27 Jul 2018, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: PRRT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

26 Jul 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397

12 Mar 2018, Gel status: 3

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.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

PRRT2 was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

PRRT2 was added to Intellectual disabilitypanel. Sources: Expert Review Green