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Genetic epilepsy syndromes

Gene: SMC1A

Green List (high evidence)

SMC1A (structural maintenance of chromosomes 1A)
EnsemblGeneIds (GRCh38): ENSG00000072501
EnsemblGeneIds (GRCh37): ENSG00000072501
OMIM: 300040, Gene2Phenotype
SMC1A is in 14 panels

5 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Sufficient evidence provided by PMID: 28166369. This group identified ten heterozygous de novo, predicted LOF, variants in the SMC1A gene. All cases were female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Cornelia de Lange syndrome 2, 300590

Publications

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 mode of inheritance: Set MOI to X-linked dominant to match Gene2Phenotype and the MOI for SMC1A on the Intellectual disability panel. So far, mostly females have gross gene alterations of SMC1A, which are likely not tolerated in males (PMID:19842212).
Created: 2 Jul 2019, 3:11 p.m. | Last Modified: 2 Jul 2019, 3:11 p.m.
Panel Version: 1.108
Comment on list classification: Updated rating from Amber to Green based on external review by Deb Pal, and a literature review. Plenty of recent papers reporting SMC1A variants causing epilepsy in female patients (e.g. PMIDs:31098032, 28677859, 28166369, 26752331,26386245,26358754). SMC1A variants can cause Cornelia de Lange syndrome (CdLS) but can also cause ID and epilepsy in the absence of CdLS features (PMID:31185419). Plus 'confirmed' rating in Gene2Phenotype for EPILEPTIC ENCEPHALOPATHY.
Created: 2 Jul 2019, 3:08 p.m. | Last Modified: 2 Jul 2019, 3:08 p.m.
Panel Version: 1.107
PMID:31185419: Oguni et al 2019 report a missense variant (c.2683C>G:pArg895Gly) of SMC1A affecting a daughter (proband) and her mother. The daughter began having epileptic seizures age 2 years 1 month, progressing into cluster seizures. The mother began to have cluster seizures age 12 and had moderate ID. Neither individual had typical CdLS morphological features. Sequencing confirmed the variant was present in daughter and mother, but not other maternal family members. Blood samples from the paternal side were unavailable.
Created: 2 Jul 2019, 2:59 p.m. | Last Modified: 2 Jul 2019, 3 p.m.
Panel Version: 1.101

Deb Pal (King's College London)

Green List (high evidence)

Amplexa CHE-114 epilepsy panel
Created: 21 Feb 2019, 3:52 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Rett-like phenotype

Publications

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

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported four unrelated cases in which seizures are a phenotypic feature.
Created: 11 Dec 2018, 2:12 p.m.

Zornitza Stark (Australian Genomics)

I don't know

XLD. Seizures reported in some patients with this syndromic disorder.
Created: 21 Aug 2018, 11:25 a.m.

Mode of inheritance
Other

Phenotypes
Cornelia de Lange syndrome 2, MIM#300590

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

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Cornelia de Lange syndrome 2, 300590
  • seizures
  • EPILEPTIC ENCEPHALOPATHY
  • Rett-like phenotype
OMIM
300040
Clinvar variants
Variants in SMC1A
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 SMC1A.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to SMC1A.

2 Jul 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: SMC1A was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

2 Jul 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: smc1a has been classified as Green List (High Evidence).

2 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: SMC1A were set to 16604071; 17273969; 31185419; 31098032

2 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: SMC1A were set to 16604071; 17273969; 31185419

2 Jul 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY to Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY; Rett-like phenotype

2 Jul 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2 300590 to Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY

2 Jul 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: SMC1A were set to 16604071; 17273969

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: XLD. Seizures reported in some

11 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: smc1a has been classified as Amber List (Moderate Evidence).

11 Dec 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SMC1A were set to 16604071

11 Dec 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SMC1A were set to

11 Dec 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SMC1A were changed from to Cornelia de Lange syndrome 2 300590

11 Dec 2018, Gel status: 2

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: SMC1A was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to SMC1A. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

SMC1A was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

SMC1A was created by Sarah Leigh