Hereditary ataxia - adult onsetGene: 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.
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
Spastic ataxia 9, autosomal recessive, OMIM:618438
gene: CHP1 was added gene: CHP1 was added to Hereditary ataxia - adult 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