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Genetic epilepsy syndromes

Gene: NSDHL

Green List (high evidence)

NSDHL (NAD(P) dependent steroid dehydrogenase-like)
EnsemblGeneIds (GRCh38): ENSG00000147383
EnsemblGeneIds (GRCh37): ENSG00000147383
OMIM: 300275, Gene2Phenotype
NSDHL is in 13 panels

4 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Comment on mode of inheritance: 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 MOI should remain as XLR.
Created: 25 Nov 2019, 9:17 p.m. | Last Modified: 25 Nov 2019, 9:17 p.m.
Panel Version: 1.467
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 and Helen Lord. 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

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

XLD CHILD syndrome (congenital hemidysplasia with ichythyosiform erthrodema and limb defects - mutations are lethal in hemizygous males) and XLR CK syndrome (mental retardation syndrome). CKS - mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features amd thin body habitus. Du Souich et al, 2009- 5 generation famIly of Russian-Doukhobor descent - 7 aff boys had onset of seizures in neonatal period - hemizygous truncating mutation . Tarpey et al, 2009 & McLarren et al, 2010 - 3 generation family with similar features 4/4 had seizures - 1 bp dup. In vitro functional expression studies showed that both mutations act as a temp sensitive hypomorphic alleles, resulting in a less severe pheno than that observed with mutations seen in CHILD syndrome. Preiksaitiene et al, 2015 - 5 generation family with aff males manifesting CK syndrome (had seizures) a missense variant was identified in this family and obligate carriers.
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
CHILD syndrome, 308050; CK syndrome, 300831

Publications

Eleanor Williams (Genomics England Curator)

Comment when marking as ready: 3 cases/variants in unrelated families where male show seizures. One SNV is missense but it segregates with the disease in the family, is predicted to affect protein function and is not found in dbSNP.
Created: 14 Nov 2018, 12:20 p.m.
Comment on list classification: 3 cases reported of variants in this gene in males with CK syndrome.
Created: 14 Nov 2018, 12:13 p.m.
NSDHL is associated with CHILD syndrome and CK syndrome in OMIM. CK syndrome is associated with seizures but CHILD syndrome is not. Also associated with CK syndrome in Gene2Phenotype.

2 unrelated families with males with hemizygous variants in NSDHL and CK syndrome reported in PMID: 21129721 (p.Lys232del and p.Arg367SerfsX33) (families originally reported in PMID 19377476 and 19842190). All affected males in both families presented with seizures.

A 3rd case is reported in PMID: 25900314. This is a 5 generation Lithuanian family with affected males manifesting clinical features of CK syndrome including seizures in the proband and 2 other males for which clinical data is available. Missense mutation p.Gly152Asp was identified in the NSDHL gene in the DNA sample of the affected male that was sequenced. Mutation carrier status was confirmed for all the obligate carriers in the family. The SNV is not found in dbSNP or in 48 samples of the general Lithuanian population. The amino acid is located in the conserved domain of the protein around the active site, although it is not one of the four residues that compose this active site. All the in silico analyses performed predict a relevant influence on the protein function.

PMID 26459993 reports a female with CHILD syndrome but no seizures.
Created: 14 Nov 2018, 12:12 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seizures are part of the phenotype of this syndromic disorder.
Created: 17 Aug 2018, 11:25 a.m.

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

Phenotypes
CK syndrome, MIM#300831

Publications

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

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • CK syndrome 300831
OMIM
300275
Clinvar variants
Variants in NSDHL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Nov 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: NSDHL was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to NSDHL.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to NSDHL.

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

14 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

14 Nov 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: NSDHL were changed from to CK syndrome 300831

14 Nov 2018, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: NSDHL was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females

14 Nov 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: NSDHL were set to

14 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: nsdhl 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 NSDHL. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

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

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

NSDHL was created by Sarah Leigh