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Genetic epilepsy syndromes

Gene: HEXB

Green List (high evidence)

HEXB (hexosaminidase subunit beta)
EnsemblGeneIds (GRCh38): ENSG00000049860
EnsemblGeneIds (GRCh37): ENSG00000049860
OMIM: 606873, Gene2Phenotype
HEXB is in 12 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

HEXB appears to have a well-characterised association with Sandhoff disease where seizures can be a feature, e.g. PMID 22848519.
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
Sandhoff disease infantile juvenile and adult forms, 268800

Rebecca Foulger (Genomics England curator)

I don't know

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
Comment on list classification: Updated rating from Amber to Green. Sufficient cases of Sandhoff disease with seizures (PMID:28553389, PMID:7626071, PMID: 30075786) for inclusion on panel.
Created: 1 Aug 2019, 12:25 p.m. | Last Modified: 1 Aug 2019, 12:25 p.m.
Panel Version: 1.185
PMID:28553389: Gowda et al., 2017 report a 1 year old boy with Sanhoff disease without hepatosplenomegaly, and a homozygous missense variant in HEXB (p.Cys534Tyr). The boy suffered from focal seizures from 11 months. A sibling died age 18 months with 'similar complaints'. Further controls or segregation analysis was not performed. The authors say the same variant was reported previously in a Japanese case which showed myoclonic epilepsy and hepatosplenomegaly (PMID:7626071).
Created: 4 Jul 2019, 2:12 p.m. | Last Modified: 4 Jul 2019, 2:12 p.m.
Panel Version: 1.125
PMID: 30075786: Tavasoli et al., 2018 studied 25 Iranian patients with Sandhoff disease. 8/25 patients had seizures (Table 2) with a mean age at presentation 5.6 months. HEXB gene mutation studies were performed in 8 patients, including 2 patients with seizures (novel HEXB variants were identified in patients 4 and 13).
Created: 4 Jul 2019, 2:05 p.m. | Last Modified: 4 Jul 2019, 2:05 p.m.
Panel Version: 1.124
PMID: 22848519. Zampieri et al., 2012 characterized 14 unrelated Sandhoff disease (SD) patients and identified 16 alleles (9 novel). 9/14 patients (from Italy, Argentina, Brazil, Turkey and China) developed seizures, although no further information is given about the phenotype. However, the authors suggest caution in interpreting molecular analyses: A second mutation was not detected in Italian patient SD3 (a deletion is likely the second allele), a novel alternative spliced HEXB mRNA variant was also present in normal control cells, and the high activity retained by the H212N change didn't correlate with the severe phenotype exhibited by patient SD11.
Created: 4 Jul 2019, 1:45 p.m. | Last Modified: 4 Jul 2019, 1:45 p.m.
Panel Version: 1.124

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Based on reviewers' comments.
Created: 11 Dec 2018, 1:21 p.m.

Zornitza Stark (Australian Genomics)

I don't know

Seizures are a reported feature, although I am having trouble ascertaining how common these are.
Created: 15 Aug 2018, 1:15 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sandhoff disease, infantile, juvenile, and adult forms, MIM#268800

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Sandhoff disease, infantile, juvenile, and adult forms, 268800
  • seizures
  • myoclonic epilepsy
OMIM
606873
Clinvar variants
Variants in HEXB
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to HEXB.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to HEXB.

1 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

4 Jul 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures to Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures; myoclonic epilepsy

4 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: HEXB were set to 2967418; 21153386; 22848519; 30075786

4 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: HEXB were set to 2967418; 21153386; 22848519

4 Jul 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures

4 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: HEXB were set to 2967418; 21153386

9 Jan 2019, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

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

9 Jan 2019, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: HEXB were set to

9 Jan 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: HEXB were changed from to Sandhoff disease, infantile, juvenile, and adult forms, 268800

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are a reported featur

11 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

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

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

HEXB was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

HEXB was created by Sarah Leigh