Adult onset leukodystrophy

Gene: HMGCL

Amber List (moderate evidence)

HMGCL (3-hydroxymethyl-3-methylglutaryl-CoA lyase)
EnsemblGeneIds (GRCh38): ENSG00000117305
EnsemblGeneIds (GRCh37): ENSG00000117305
OMIM: 613898, Gene2Phenotype
HMGCL is in 11 panels

7 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Created: 4 May 2024, 5:32 p.m. | Last Modified: 4 May 2024, 5:43 p.m.
Panel Version: 4.3

Sarah Leigh (Genomics England Curator)

I don't know

As HMG-CoA lyase deficiency (OMIM:246450) has an onset in infancy or childhood, it may be inappropriate to have HMGCL as a green gene on this panel - Adult onset leukodystrophy. PMID: 28583327 reports 37 cases of HMG-CoA lyase deficiency where the first symptoms are reported from birth to 4 years of age.
Created: 12 Oct 2023, 3:32 p.m. | Last Modified: 12 Oct 2023, 3:32 p.m.
Panel Version: 3.20

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Onset is typically in infancy.
Created: 21 Jun 2020, 6:27 a.m. | Last Modified: 21 Jun 2020, 6:27 a.m.
Panel Version: 1.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, MIM# 246450

Publications

David Lynch (UCL Institute of Neurology)

Green List (high evidence)

Catherine Snow (Genomics England)

I don't know

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, 246450

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating uploaded from file (Consensus gene list for R62 Adult-Onset Leukodystrophy - Leeds.xlsx) submitted by Ian Berry (Leeds Genetics Laboratory) on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group. Phenotype and MOI not submitted.
Created: 4 Jul 2019, 4:32 p.m. | Last Modified: 4 Jul 2019, 4:32 p.m.
Panel Version: 0.10

Ian Berry (Leeds Genetics Laboratory)

Green List (high evidence)

Included all genes listed in clinical cases in Lynch et al 2015 PMID:28334938 and Ayrignac et al. 2015 PMID: 25527826. Included all genes with clear adult onset listed in Vanderver 2017 PMID:27159321 and Ahmed et al. 2017 PMID:24357685. A small number of genes from these resources were omitted, particularly those with limited or single case reports referenced in Ahmed et al, those with a metabolic basis (that could be determined by standard metabolic assays), and recessive diseases where the likelihood of encountering incidental carrier status is far more likely than finding a diagnosis e.g. Cockayne syndrome. Due to variable expressivity and potential later onset of phenotype in hypomorphic cases, peroxisomal biogenesis disorders OMIM phenotypic Series PS214100 and GeneReviews PMID:20301621 included.
Created: 4 Jul 2019, 4:06 p.m. | Last Modified: 4 Jul 2019, 4:06 p.m.
Panel Version: 0.9

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
  • Yorkshire and North East GLH
Phenotypes
  • HMG-CoA lyase deficiency, OMIM:246450
  • 3-hydroxy-3-methylglutaric aciduria, MONDO:0009520
OMIM
613898
Clinvar variants
Variants in HMGCL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

4 May 2024, Gel status: 2

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q4_23_demote_amber was removed from gene: HMGCL. Tag Q4_23_expert_review was removed from gene: HMGCL.

4 May 2024, Gel status: 2

Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Amber was added to HMGCL. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

12 Oct 2023, Gel status: 3

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q4_23_demote_amber tag was added to gene: HMGCL. Tag Q4_23_expert_review tag was added to gene: HMGCL.

12 Oct 2023, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: HMGCL were set to 27159321; 25527826; 28334938; 20301621; 24357685

12 Oct 2023, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: HMGCL were changed from HMG-CoA lyase deficiency, 246450 to HMG-CoA lyase deficiency, OMIM:246450; 3-hydroxy-3-methylglutaric aciduria, MONDO:0009520

24 Jul 2019, Gel status: 3

Set mode of inheritance, Set Phenotypes

Catherine Snow (Genomics England)

Mode of inheritance for gene HMGCL was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes HMG-CoA lyase deficiency, 246450 for gene: HMGCL

4 Jul 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene HMGCL were changed from to 27159321; 25527826; 28334938; 20301621; 24357685

4 Jul 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to HMGCL. Rating Changed from Red List (low evidence) to Green List (high evidence)

4 Jul 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to HMGCL.

4 Jul 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: HMGCL was added gene: HMGCL was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH Mode of inheritance for gene: HMGCL was set to