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| Cerebellar and Pontocerebellar Hypoplasia v1.34 | CHP1 | Zornitza Stark Marked gene: CHP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebellar and Pontocerebellar Hypoplasia v1.34 | CHP1 | Zornitza Stark Gene: chp1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebellar and Pontocerebellar Hypoplasia v1.34 | CHP1 | Zornitza Stark Publications for gene: CHP1 were set to PMID: 29379881, 32787936 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebellar and Pontocerebellar Hypoplasia v1.33 | CHP1 | Chirag Patel Classified gene: CHP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebellar and Pontocerebellar Hypoplasia v1.33 | CHP1 | Chirag Patel Gene: chp1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebellar and Pontocerebellar Hypoplasia v1.32 | CHP1 |
Chirag Patel gene: CHP1 was added gene: CHP1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHP1 were set to PMID: 29379881, 32787936 Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM #618438 Review for gene: CHP1 was set to GREEN Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family. Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse. Sources: Literature |
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