Likely inborn error of metabolism - targeted testing not possible
Gene: CLPBThe mode of inheritance of this gene has been updated followingNHS Genomic Medicine Service approval.Created: 14 Mar 2022, 2:05 p.m. | Last Modified: 14 Mar 2022, 2:05 p.m.
Panel Version: 2.229
Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.
Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype overlapped with that observed in the recessive disease including neurodevelopmental delay, seizures, 3-MGA-uria, and neutropenia. Some functional studies of heterozygous variants were performed.Created: 15 Nov 2021, 2:36 p.m. | Last Modified: 15 Nov 2021, 2:36 p.m.
Panel Version: 2.198
Association between bi-allelic variants and disease is well established.
Mono-allelic variants: six unrelated individuals reported with de novo variants and neutropaenia, epilepsy, developmental issues, and 3-methylglutaconic aciduria.Created: 8 Jul 2021, 8:14 a.m. | Last Modified: 8 Jul 2021, 8:14 a.m.
Panel Version: 2.150
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271
Publications
Comment on list classification: Is currently green on the intellectual disability panel, as well as being rated as green by the reviewer who added it. It is a confirmed DD gene for 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia.Created: 15 Feb 2016, 11:03 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
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.
Source NHS GMS was added to CLPB. Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLPB were set to 25597510; 25597511; 25650066; 25595726
Tag Q4_21_MOI tag was added to gene: CLPB.
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 with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Checked against super panel made up of the panel constituents. Ready to promote to version 1.
Added phenotypes 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder for gene: CLPB Publications for gene CLPB were changed from PMID: 25597510; PMID: 25650066; PMID: 25597511; PMID: 25595726 to 25597510; 25597511; 25650066; 25595726
gene: CLPB was added gene: CLPB was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: CLPB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLPB were set to PMID: 25597510; PMID: 25650066; PMID: 25597511; PMID: 25595726 Phenotypes for gene: CLPB were set to 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder