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Intellectual disability

Gene: PYCR1

Green List (high evidence)

PYCR1 (pyrroline-5-carboxylate reductase 1)
EnsemblGeneIds (GRCh38): ENSG00000183010
EnsemblGeneIds (GRCh37): ENSG00000183010
OMIM: 179035, Gene2Phenotype
PYCR1 is in 12 panels

5 reviews

Helen Brittain (Genomics England Curator)

Comment when marking as ready: Overall there are sufficient cases with variants in this gene and ID for inclusion, in addition to a supportive animal model.
Created: 13 Nov 2017, 4:26 p.m.

Caroline Wright (Sanger)

Red List (low evidence)

Phenotypes
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIB

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: Changed from Amber to Green after internal clinical review. The genereview section relating to PYCR1-related cutis laxa suggests 95% are associated with ID and although the majority are offspring of consanguineous unions this gene is still recommended as being rated as green.
Created: 31 Oct 2017, 2:32 p.m.
It is noted in Genereviews that ID being a feature but not characteristic clinical finding for Cutis laxa, autosomal recessive, type IIB. In a recent (2017) Mouse model paper they show mutations in the PYCR1 gene cause cutis laxa with progeroid features and mental retardation (PMID: 27796797). PMID: 27756598_ (2017) describes one large family with two affecteds with ID and one case PMID: 26516448_ was described with ID.
Created: 31 Oct 2017, 11:34 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cutis laxa, autosomal recessive, type IIB, 612940; ARCL2B

Publications

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_gilissen_2014_known . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 8:11 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_red_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, 1:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Lu Raymond (university of cambridge )

Red List (low evidence)

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cutis laxa, autosomal recessive, type IIB, 612940
  • ARCL2B
  • Intellectual disability
OMIM
179035
Clinvar variants
Variants in PYCR1
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 PYCR1.

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.

8 Jan 2018, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for PYCR1 were set to Cutis laxa, autosomal recessive, type IIB, 612940; ARCL2B; Intellectual disability

29 Nov 2017, Gel status: 4

Added New Source, Set mode of inheritance, Set publications

Ellen McDonagh (Genomics England Curator)

Expert Review Green was added to PYCR1. Panel: Intellectual disability Model of inheritance for gene PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene PYCR1 was set to ['27756598', '19401719', '27796797', '26516448']

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PYCR1 was added to Intellectual disabilitypanel. Source: Expert Review Red

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PYCR1 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen