Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: CLPBThe mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:59 a.m. | Last Modified: 8 Mar 2022, 10:59 a.m.
Panel Version: 2.532
Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.
Association between biallelic variants and disease is well established, with more than 10 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease, including moderate to severe congenital/early-onset neutropenia in 5/6 cases. Some functional studies of heterozygous variants were performed.Created: 15 Nov 2021, 4:20 p.m. | Last Modified: 15 Nov 2021, 4:25 p.m.
Panel Version: 2.496
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CLPB .PanelApp HGNC gene symbol check: CLPB . IUIS Disease: 3-Methylglutaconic aciduria . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N. IUIS Associated features: Neurocognitive developmental aberrations, microcephaly, hypoglycemia, hypotonia, ataxia, seizures, cataracts, IUGR. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Congenital NeutropeniasCreated: 2 Jul 2018, 10:35 a.m.
Comment on publications: Capo-Chichi et al. (2015) PMID: 25650066 identified a homozygous truncating mutation in the CLPB gene (616254.0010) that segregated with the disorder in the family. The mutation was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencingCreated: 4 Jun 2018, 1:53 p.m.
Comment on list classification: changed from Amber to Green enough evidence to support immune dysfunction -recurrent or severe infection is observed in a large number of unrelated patients described with 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) see PMID: 25597510, 25597511,25650066, 28687938, 26916670 and with over 14 pathogenic variants with a range of molecular consequences.Created: 4 Jun 2018, 1:48 p.m.
Comment on publications: Wortmann et al. (2015) PMID:25597510 described 14 individuals from 9 unrelated families with 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia, which is also referred to as 3-methylglutaconic aciduria type VII, and identified 14 different homozygous or compound heterozygous mutations in the CLPB gene. Then, Saunders et al. (2015) PMID: 25597511 further described patients, including 2 sibs, of Greenlandic descent identifying a homozygous missense mutation in the CLPB gene.Created: 4 Jun 2018, 1:48 p.m.
Comment on phenotypes: added MIMid from OMIM and phenotype from Orphanet. The phenotype is highly variable: most patients have infantile onset of a progressive encephalopathy with various movement abnormalities and delayed psychomotor development, although rare patients with normal neurologic development have been reported.
The neurological presentation ranges from normal development without intellectual deficits to a severe and progressive encephalopathy associated with muscular hypertonia, progressive brain atrophy and movement disorder. Additionally, cataracts, neutropenia, infections and leukaemia are reported. All patients share an elevated urinary excretion of 3-methylglutaconic acid (3-MGA) as a characteristic biomarker ( Pronicka et al. 2017 PMID: 28687938 )Created: 4 Jun 2018, 1:35 p.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 20 Apr 2018, 12:25 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CLPB, GRID_Gene_Symbol: CLPB, GRID_Transcript_ENS_Community submitted: ENST00000294053, GRID_Transcript_RefSeq: NM_030813.5, GRID_Transcript_ENS_used_on_Production: ENST00000294053Created: 17 Apr 2018, 12:12 p.m.
Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271 to 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271; 3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM: 619835; Neutropenia, severe congenital, 9, autosomal dominant, OMIM: 619813
Tag Q4_21_MOI was removed from gene: CLPB.
Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q4_21_MOI tag was added to gene: CLPB.
Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066; 26916670
Mode of inheritance for gene: CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271; 3-methylglutaconic aciduria, type 7; Recurrent or severe infection; Neurocognitive developmental aberrations, microcephaly, hypoglycemia, hypotonia, ataxia, seizures, cataracts, IUGR; Congenital defects of phagocyte number or function to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Source NHS GMS was added to CLPB.
Source North West GLH was added to CLPB.
Source London North GLH was added to CLPB.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Phenotypes for gene CLPB were set to 3-methylglutaconic aciduria, type VII, 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271, 3-methylglutaconic aciduria, type 7, Recurrent or severe infection, Neurocognitive developmental aberrations, microcephaly, hypoglycemia, hypotonia, ataxia, seizures, cataracts, IUGR, Congenital defects of phagocyte number or function
IUIS Classification February 2018 was added to CLPB. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to CLPB. Panel: Primary immunodeficiency disorders
Gene: clpb has been classified as Green List (High Evidence).
Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066; 26916670
Phenotypes for gene: CLPB were set to 3-methylglutaconic aciduria, type VII; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271; 3-methylglutaconic aciduria, type 7; Recurrent or severe infection
Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066
Gene: clpb has been classified as Green List (High Evidence).
Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066
Phenotypes for gene: CLPB were set to 3-methylglutaconic aciduria, type VII; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271; 3-methylglutaconic aciduria, type 7
Expert Review Amber was added to CLPB. Panel: Primary immunodeficiency disorders
Phenotypes for gene CLPB were set to 3-methylglutaconic aciduria, type VII
CLPB was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
CLPB was created by Louise Daugherty