Hereditary spastic paraplegia

Gene: KDM5C

Amber List (moderate evidence)

KDM5C (lysine demethylase 5C)
EnsemblGeneIds (GRCh38): ENSG00000126012
EnsemblGeneIds (GRCh37): ENSG00000126012
OMIM: 314690, Gene2Phenotype
KDM5C is in 8 panels

4 reviews

Louise Daugherty (Genomics England Curator)

I don't know

Gene to be reviewed again after the GMS Neurology specialist test group have reviewed and agreed rating of gene on the Hereditary spastic paraplegia - childhood onset panel on May 2019
Created: 3 May 2019, 8:35 a.m.

Rebecca Foulger (Genomics England curator)

Added 'watchlist' tag.
Created: 8 Jan 2019, 3:15 p.m.
Comment on list classification: Updated rating from Red to Amber. Gene added to panel and rated Red by Chris Buxton (Bristol NHS). MIM:300534 is characterized by ID, progressive spastic paraplegia, short stature, microcephaly, and dysmorphic facial appearance. Chris Buxton reports 2 families from the literature (PMIDs10982473; 15586325; 26919706) with KDM5C variants and spastic paraplegia symptoms. Therefore Amber awaiting further cases.
Created: 8 Jan 2019, 3:15 p.m.
PMID:26919706 investigated a family of 3 boys with ID and among them identified two different variants in KDM5C: Two affected boys have c.633delG and the other has c.631delC. The boys presented with severe DD, progressive spasticity (predominantly in the lower limbs), epilepsy and subclinical hypothyroidism. The mother has two different frameshift mutations: a heterozygous germline mutation, c.631delC, and a low-prevalence somatic mutation, c.633delG.
Created: 8 Jan 2019, 3:13 p.m.
PMID:15586325 (Jensen 2005) identifed a L731F variant in 4 members of a family with X-linked complicated spastic paraplegia previously described by Claes et al (2000, PMID:10982473).
Created: 8 Jan 2019, 3:13 p.m.

Sarah Leigh (Genomics England Curator)

Comment on list classification: This gene is awaiting curator evaluation and rating.
Created: 19 Dec 2018, 2:12 p.m.

Chris Buxton (North Bristol NHS Trust)

Red List (low evidence)

Claes (2000, 10982473) reported candidate HSP locus Xp21.1-Xq21.3. Jensen (2005, 15586325) identified as JARID1C(syn)/KDM5C gene: c.2191C>T Leu731Phe. 4 males in same pedigree: two generations present with severe MR, slowly progressive spastic paraplegia, facial hypotonia, and maxillary hypoplasia. Additional features are aggressive behavior and strabismus;

Fujita (2016, 26919706). Two different fs deletion variants. maternal reversion mechanims? Progressive spasticity component to phenotype.

Currently diagnostic on Sheffield's HSP panel
Sources: Literature
Created: 27 Nov 2018, 1:34 p.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
Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism

Publications

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 Amber
Phenotypes
  • Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534
  • Intellectual disability
  • developmental delay
  • progressive spasticity
  • epilepsy
  • hypothyroidism
Tags
watchlist
OMIM
314690
Clinvar variants
Variants in KDM5C
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

8 Jan 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: KDM5C.

8 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: kdm5c has been classified as Amber List (Moderate Evidence).

8 Jan 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: KDM5C were changed from Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism to Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism

19 Dec 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: kdm5c has been classified as Red List (Low Evidence).

27 Nov 2018, Gel status: 0

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

Chris Buxton (North Bristol NHS Trust)

gene: KDM5C was added gene: KDM5C was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: KDM5C 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: KDM5C were set to 10982473; 15586325; 26919706 Phenotypes for gene: KDM5C were set to Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism Penetrance for gene: KDM5C were set to unknown Review for gene: KDM5C was set to RED