Hereditary ataxia
Gene: CHP1
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
Only 2 families reported to date. One additional unpublished family with ID, spasticity and severe disease course.
Sources: LiteratureCreated: 20 Aug 2021, 3:36 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
ataxia; ID
Publications
Publications for gene: CHP1 were set to 32787936; 29379881
Tag watchlist tag was added to gene: CHP1.
Gene: chp1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: CHP1 were changed from ataxia; ID to Spastic ataxia 9, autosomal recessive, OMIM:618438
gene: CHP1 was added gene: CHP1 was added to Hereditary ataxia. Sources: Literature Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHP1 were set to 32787936; 29379881 Phenotypes for gene: CHP1 were set to ataxia; ID Review for gene: CHP1 was set to AMBER