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Genetic Epilepsy

Gene: ZDHHC15

Red List (low evidence)

ZDHHC15 (zinc finger DHHC-type containing 15)
EnsemblGeneIds (GRCh38): ENSG00000102383
EnsemblGeneIds (GRCh37): ENSG00000102383
OMIM: 300576, Gene2Phenotype
ZDHHC15 is in 3 panels

3 reviews

Krithika Murali (Victorian Clinical Genetics Services)

Red List (low evidence)

1 reported case of an 18 yo M with hypotonic cerebral palsy, focal-onset epilepsy, cortical visual impairment, intellectual disability, autism spectrum disorder, anxiety, and aggressive behaviors with hemizygous p.H158R variant shown to affect protein function in yeast complementation assay (Lewis et al Neurology Genetics 2021 PMID 34345675).

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Other background info:

Protein function of x4 ZDHHC15 variants assessed by Lewis et al. x2 variants identified through Jin et al Nat Genet 2020 (PMID 32989326) - maternally inherited p.H158R and p.L13P. x1 identified through Gene Matcher p.S330P and x1 through GeneDx maternally inherited p.K115R. Only p.H158R variant shown to affect protein function. In Drosophilia model LoF variants caused flight and co-ordinated movement defects supporting role in motor dysfunction.

Conflicting evidence for ID phenotype

1 case with intellectual disability and balanced translocation with breakpoints near the ZDHHC15 gene - functional studies showing absence of ZDHHC15 transcript variants. This patient showed skewed lyonization, with 100% inactivation of the normal X chromosome. PMID: 15915161

1 case with NO intellectual disability and balanced translocation with breakpoints in the ZDHHC15 gene - functional studies showing no gene expression in the patient's peripheral blood (PMID 26290131)
Sources: Expert list, Literature
Created: 5 Oct 2021, 4:47 a.m.

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
Mental retardation X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy

Publications

Daniel Flanagan (Victorian Clinical Genetics Services)

Red List (low evidence)

Hemizygous missense (p.H158R) identified in a patient with a mixed neurodevelopmental phenotype that included cerebral palsy, intellectual disability, autism spectrum disorder, and epilepsy. In yeast, vacuolar fragmentation phenotype was not rescued by yeast expressing the variant. In Drosophila, mutant flies had increased average time to execute a coordinated axial twisting task and were less likely to initiate flights.
No PubMed ID available, Mutation in ZDHHC15 Leads to Hypotonic Cerebral Palsy, Autism, Epilepsy, and Intellectual Disability. https://ng.neurology.org/content/7/4/e602
Created: 2 Aug 2021, 7:11 a.m. | Last Modified: 2 Aug 2021, 7:11 a.m.
Panel Version: 0.8602

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

Phenotypes
cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

no OMIM phenotype number.
Conflicting evidence:
1 case with intellectual disability and balanced translocation with breakpoints near the ZDHHC15 gene - functional studies showing absence of ZDHHC15 transcript variants.
1 case with NO intellectual disability and balanced translocation with breakpoints in the ZDHHC15 gene - functional studies showing no gene expression in the patient's peripheral blood.
Created: 4 Mar 2020, 1:30 a.m. | Last Modified: 4 Mar 2020, 1:30 a.m.
Panel Version: 0.1621

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

Phenotypes
Intellectual disability, X-linked 91, 300577

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
  • Expert Review Red
  • Literature
  • Expert list
  • Expert Review Red
  • Victorian Clinical Genetics Services
Phenotypes
  • Intellectual disability, X-linked 91, 300577
OMIM
300576
Clinvar variants
Variants in ZDHHC15
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 May 2024, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: ZDHHC15 were changed from Mental retardation X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy to Intellectual disability, X-linked 91, 300577

5 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: zdhhc15 has been classified as Red List (Low Evidence).

5 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: zdhhc15 has been classified as Red List (Low Evidence).

5 Oct 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Krithika Murali (Victorian Clinical Genetics Services)

gene: ZDHHC15 was added gene: ZDHHC15 was added to Genetic Epilepsy. Sources: Expert list,Literature Mode of inheritance for gene: ZDHHC15 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: ZDHHC15 were set to 34345675; 15915161; 26290131; 32989326 Phenotypes for gene: ZDHHC15 were set to Mental retardation X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy Review for gene: ZDHHC15 was set to RED