| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hereditary ataxia v1.241 | CHP1 | Arina Puzriakova edited their review of gene: CHP1: Changed rating: AMBER; Changed publications to: 23904602, 29379881, 32787936; Changed phenotypes to: Spastic ataxia 9, autosomal recessive, OMIM:618438; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.241 | CHP1 |
Arina Puzriakova changed review comment from: 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 GMS panels, but currently the evidence only suffices for an Amber rating for each (added watchlist tag).; to: 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). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.241 | CHP1 | Arina Puzriakova Publications for gene: CHP1 were set to 32787936; 29379881 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.240 | CHP1 | Arina Puzriakova Tag watchlist tag was added to gene: CHP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.240 | CHP1 | Arina Puzriakova Classified gene: CHP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.240 | CHP1 |
Arina Puzriakova Added comment: 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 GMS panels, but currently the evidence only suffices for an Amber rating for each (added watchlist tag). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.240 | CHP1 | Arina Puzriakova Gene: chp1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.239 | CHP1 | Arina Puzriakova Phenotypes for gene: CHP1 were changed from ataxia; ID to Spastic ataxia 9, autosomal recessive, OMIM:618438 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.238 | CHP1 |
Julia Baptista 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 Added comment: Only 2 families reported to date. One additional unpublished family with ID, spasticity and severe disease course. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||