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Primary immunodeficiency

Gene: CLPB

Green List (high evidence)

CLPB (ClpB homolog, mitochondrial AAA ATPase chaperonin)
EnsemblGeneIds (GRCh38): ENSG00000162129
EnsemblGeneIds (GRCh37): ENSG00000162129
OMIM: 616254, Gene2Phenotype
CLPB is in 13 panels

4 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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 Neutropenias
Created: 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 sequencing
Created: 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: ENST00000294053
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • GRID V2.0
Phenotypes
  • 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
OMIM
616254
Clinvar variants
Variants in CLPB
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to CLPB.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to CLPB.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to CLPB.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

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

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to CLPB. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to CLPB. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: clpb has been classified as Green List (High Evidence).

4 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066; 26916670

4 Jun 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

4 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066

4 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: clpb has been classified as Green List (High Evidence).

4 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CLPB were set to 27891836; 25597510; 28687938; 25597511; 25650066

4 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to CLPB. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene CLPB were set to 3-methylglutaconic aciduria, type VII

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

CLPB was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

CLPB was created by Louise Daugherty