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Genetic epilepsy syndromes

Gene: EFHC1

Amber List (moderate evidence)

EFHC1 (EF-hand domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000096093
EnsemblGeneIds (GRCh37): ENSG00000096093
OMIM: 608815, Gene2Phenotype
EFHC1 is in 2 panels

7 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

This gene appears to be associated with various epilepsy phenotypes, and the evidence comes from various sources. Additionally, there are several cases of EFHC1 being associated with juvenile myoclonic epilepsy in PMID 28370826.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Epilepsy, juvenile absence, susceptibility to, 1}, 607631 ; {Myoclonic epilepsy, juvenile, susceptibility to, 1}, 254770

Publications

Rebecca Foulger (Genomics England curator)

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.
Created: 13 Aug 2019, 4:15 p.m. | Last Modified: 15 Aug 2019, 8:05 a.m.
Panel Version: 1.222
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: Alison Callaway and John Taylor. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
PMID:29750216: Thounaojam et al., 2017 studied 63 Indian patients from 63 independent families with Juvenile myoclonic epilepsy (JME) and found 4 heterozygous coding variants (R221C, R260Q, R294H and R244STOP) and 1 homozygous and one heterozygous coding variant (R159W, which is considered a polymorphism). Lack of family samples meant the mode of inheritance couldn't be followed up.
Created: 1 Jul 2019, 1:09 p.m. | Last Modified: 1 Jul 2019, 1:09 p.m.
Panel Version: 1.85
PMID:31056551: Heyne et al., 2019 performed a large-scale analysis of previously-sequenced variants in individuals with a 'neurodevelopmental disorder with epilepsy. They show that EFHC1 showed equal frequencies of ultra-rare variants in cases and controls supporting the existing evidence that EFHC1 may not be truly associated with epilepsy.
Created: 1 Jul 2019, 1:09 p.m. | Last Modified: 1 Jul 2019, 1:09 p.m.
Panel Version: 1.85
PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. All variants were missense. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).
Created: 1 Jul 2019, 1:08 p.m. | Last Modified: 1 Jul 2019, 1:08 p.m.
Panel Version: 1.85

Sarah Leigh (Genomics England Curator)

Comment on list classification: As this gene is associated with susceptibility to juvenile absence epilepsy (MIM 607631) and juvenile myoclonic epilepsy 1 (MIM 254770), EFHC1 has been rated at amber in consultation with Arianna Tucci (GEL Clinical Fellow).
Created: 14 Nov 2018, 9:06 p.m.
Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 7 variants identified in unrelated cases, due to issues of penetrance the pathogenicity classification of the variants is not well established. However, a null mouse model is supportive of the association of EFHC1 with epilepsy (PMID 19147686).
Created: 21 Jun 2018, 8:41 a.m.

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
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Wessex and West Midlands GLH
  • NHS GMS
  • NIHRBR-RD Consortium SPEED_v3.0_20170404
  • Expert list
  • Literature
Phenotypes
  • {Epilepsy, juvenile absence, susceptibility to, 1} 607631
  • {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770
OMIM
608815
Clinvar variants
Variants in EFHC1
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

15 Aug 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: efhc1 has been classified as Amber List (Moderate Evidence).

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to EFHC1.

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to EFHC1.

1 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686; 28370826

1 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Sarah Leigh: Comment on list classification

14 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: efhc1 has been classified as Amber List (Moderate Evidence).

14 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: efhc1 has been classified as Amber List (Moderate Evidence).

17 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: efhc1 has been classified as Green List (High Evidence).

26 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to EFHC1. Panel: Genetic Epilepsy Syndromes

21 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: efhc1 has been classified as Amber List (Moderate Evidence).

21 Jun 2018, Gel status: 2

Added New Source, Set penetrance

Sarah Leigh (Genomics England Curator)

Expert list was added to EFHC1. Panel: Genetic Epilepsy Syndromes Phenotypes for gene EFHC1 were set to {Epilepsy, juvenile absence, susceptibility to, 1} 607631, {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770

21 Jun 2018, Gel status: 2

Removed Source, Added New Source, Set penetrance, Set penetrance

Sarah Leigh (Genomics England Curator)

Source Expert was removed from EFHC1. Panel: Genetic Epilepsy Syndromes Literature was added to EFHC1. Panel: Genetic Epilepsy Syndromes Phenotypes for gene EFHC1 were set to {Epilepsy, juvenile absence, susceptibility to, 1} 607631, {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770 Penetrance for gene EFHC1 was set to Incomplete

21 Jun 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: EFHC1 were set to {Epilepsy, juvenile absence, susceptibility to, 1} 607631; {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770

21 Jun 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686

21 Jun 2018, Gel status: 2

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: EFHC1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

21 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: efhc1 has been classified as Amber List (Moderate Evidence).

4 Apr 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

EFHC1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert,Expert Review Red

4 Apr 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

EFHC1 was created by Sarah Leigh