Genes in panel
STRs in panel
Prev Next

Genetic epilepsy syndromes

Gene: HLCS

Amber List (moderate evidence)

HLCS (holocarboxylase synthetase)
EnsemblGeneIds (GRCh38): ENSG00000159267
EnsemblGeneIds (GRCh37): ENSG00000159267
OMIM: 609018, Gene2Phenotype
HLCS is in 12 panels

8 reviews

Rebecca Foulger (Genomics England curator)

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
Created: 25 Nov 2019, 8:53 p.m. | Last Modified: 25 Nov 2019, 8:53 p.m.
Panel Version: 1.445
PMID:27114915 (Donti et al., 2016) describe a cohort of 5 patients. Case 5 had focal seizures age 5 months which have continued since. He has compound het variants in HLCS (N570K and c.1519+5G>A). The authors note that the phenotypic spectrum of HCLS is broad, from intractable seizures and ID to normal growth and development.
Created: 21 Nov 2019, 2:21 p.m. | Last Modified: 21 Nov 2019, 2:21 p.m.
Panel Version: 1.416
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Amber.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

AR Holocarboxylase synthetase deficiency - charecterised by metabolic acidosis, lethargy, hypotonia, convusions and dermatisis. Most patients present in newborn or early infantile period. Suzuki et al, 2005 - review - 30 mutations reported to date - no detailed clinical info provided. On OMIM no mention of seizures in any of the clinical features described. In Donti et al, 2016 - 5 unrealted patients - 1/5 has seizures. It's possible that early diagnosis and treatment have stopped the development of seizures. Would these all be picked up on newborn biochemical screening ? whether should be in panel.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Holocarboxylase synthetase deficiency, 253270

Publications

Louise Daugherty (Genomics England Curator)

Comment on list classification: changed rating from Red to Green as suggested by external reviewer. . Publications support gene-disease association and rating of this gene to Green.
Created: 1 Oct 2018, 4:36 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seizures are part of the phenotype in this metabolic disorder.
Created: 15 Aug 2018, 1:24 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Holocarboxylase synthetase deficiency, MIM#253270

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

Amy McTague (UCL Institute of Child Health)

Red List (low evidence)

Natalie Trump (NHS - Great Ormond Street Hospital)

Red List (low evidence)

Manju Kurian (UCL-Institute of Child Health)

Red List (low evidence)

Richard Scott (North Thames GMC/UCL)

Red List (low evidence)

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Wessex and West Midlands GLH
  • NHS GMS
  • Victorian Clinical Genetics Services
  • Expert
Phenotypes
  • Holocarboxylase synthetase deficiency, 253270
OMIM
609018
Clinvar variants
Variants in HLCS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Nov 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: hlcs has been classified as Amber List (Moderate Evidence).

7 Nov 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: HLCS were set to

7 Nov 2019, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: HLCS were changed from to Holocarboxylase synthetase deficiency, 253270

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to HLCS.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to HLCS.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are part of the pheno

16 Oct 2018, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: HLCS was changed from to BIALLELIC, autosomal or pseudoautosomal

1 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to HLCS. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

Victorian Clinical Genetics Services was added to HLCS. Panel: Genetic Epilepsy Syndromes

4 Apr 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

HLCS was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert

4 Apr 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

HLCS was created by Sarah Leigh