Intellectual disability - microarray and sequencing
Gene: PRRT2New 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
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
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 tagCreated: 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 IDCreated: 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 IDCreated: 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 AmberCreated: 26 Jul 2018, 1:30 p.m.
biallelic phenotype includes IDCreated: 26 Jul 2018, 1:16 p.m.
phenotypes associated to biallelic phenotype with includes IDCreated: 26 Jul 2018, 1:16 p.m.
Comment on publications: added publications to support the ID phenotypeCreated: 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:21937992Created: 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
Not convinced intellectual disability is part of the phenotypeCreated: 20 Jun 2018, 3:19 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME
Publications
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 functionCreated: 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 TrustCreated: 19 Jul 2017, 1:12 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439
Gene: prrt2 has been classified as Amber List (Moderate Evidence).
Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439
Phenotypes for gene: PRRT2 were set to Epilepsy; mental retardation; movement disorders; paroxysmal disorder; Autosomal recessive mental retardation
Mode of inheritance for gene: PRRT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: PRRT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: PRRT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397
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.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
PRRT2 was created by ellenmcdonagh
PRRT2 was added to Intellectual disabilitypanel. Sources: Expert Review Green