Hereditary spastic paraplegia - childhood onset

Gene: CHP1

Amber List (moderate evidence)

CHP1 (calcineurin like EF-hand protein 1)
EnsemblGeneIds (GRCh38): ENSG00000187446
EnsemblGeneIds (GRCh37): ENSG00000187446
OMIM: 606988, Gene2Phenotype
CHP1 is in 5 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: New gene added by Julia Baptista (RD&E_NHS). Rating Amber, awaiting further cases to better delineate phenotypes and for clarification regarding the age of onset.
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Two unrelated families, each with two affected sibs presenting ataxia, associated with different biallelic variants in the CHP1 gene (PMID: 29379881; 32787936). Other features include intellectual disability (3/4), cerebellar atrophy (3/4), spastic paraplegia (3/4), and neuropathy (2/4).

In vitro studies of one variant showed mutant CHP1 fails to integrate into functional complexes and impairs membrane localisation of the Na+/H+ transporter NHE1. Zebrafish and mouse models recapitulate human phenotypes such as movement defects (including ataxia), cerebellar hypoplasia, and axon abnormalities (PMID: 23904602; 29379881).

However, there are some notable differences between the two families. The age at onset differs considerably with one sib pair presenting with ataxia and cognitive decline in middle age (PMID: 32787936), in contrast to the other sibs who had infantile-onset ataxia and intellectual disability (PMID: 29379881).

CHP1 has been added to both adult and childhood-onset ataxia and spasticity GMS panels, but currently the evidence only suffices for an Amber rating for each (added watchlist tag).
Created: 25 Aug 2021, 1:33 p.m. | Last Modified: 25 Aug 2021, 1:35 p.m.
Panel Version: 1.241

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic ataxia 9, autosomal recessive, OMIM:618438

Publications

Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

I don't know

Only 2 families reported to date. One additional unpublished family with ID, spasticity and severe disease course.
Sources: Literature
Created: 20 Aug 2021, 3:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ataxia; ID

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Amber
Phenotypes
  • Spastic ataxia 9, autosomal recessive, OMIM:618438
Tags
watchlist
OMIM
606988
Clinvar variants
Variants in CHP1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Aug 2021, Gel status: 2

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

Arina Puzriakova (Genomics England Curator)

gene: CHP1 was added gene: CHP1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature watchlist tags were added to gene: CHP1. Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHP1 were set to 23904602; 29379881; 32787936 Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM:618438