Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) lead to SCA15, SCA16, and SCA29. To date, only a few families with SCA29 have been reported. A three-generation Chinese family including four affected persons and two unaffected persons were enrolled in this study. We conducted whole-exome sequencing (WES) of the proband DNA initially to find the causal gene. We ascertained the family with autosomal dominant type of congenital nonprogressive cerebellar ataxia (CNPCA) associated with delayed motor and cognitive impairment. WES study was performed with two patients and identified c.1207-2A-T transition, in exon 14 of ITPR1, which was a splicing mutation. Sanger sequencing showed that four patients within this family carried the mutation and two unaffected members did not carry it. The results showed that the novel splicing mutation of ITPR1 was the causative gene for SCA29. In conclusion, we identified a novel SCA29 causative splicing mutation of ITPR1 in a Chinese family. We suggest ITPR1 gene analysis shall be a priority for diagnosis of patients with early-onset CNPCA. Our study demonstrated that whole-exome sequencing might rapidly improve the diagnosis of genetic ataxias.
Cerebellum 2018 Jun
PMID:Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family. 2919 76

The Inositol 1,4,5-trisphosphate receptor type 1 protein (Ip3r1) performs an essential role for the induction of cerebellar long-term depression. Here, I describe the use of RT-PCR, qPCR, western blotting and immunohistochemistry to assay Ip3r1 gene expression and localize Ip3r1 protein in the hindbrain of the elasmobranch fish, Leucoraja erinacea. Elasmobranchs are representatives of the most basal, yet extant lineage of gnathostomes, or jawed vertebrates. The cerebellum is a synapomorphy for gnathostomes and thus elasmobranch cerebellar physiology may serve as a proxy for the ancestral state of other jawed vertebrates. LeIp3r1 is selectively expressed in the cerebellum of the little skate and the resultant protein is localized to Purkinje cells. If Ip3r1 performs the same functions in the skate cerebellum as in the mammalian cerebellum, then parallel fiber-Purkinje cell long-term depression through Ip3r1 mediated intracellular calcium regulation may be a conserved feature of cerebellar physiology. Cerebellum and surrounding hindbrain regions termed cerebellum-like structures share a common developmental genetic toolkit. LeIp3r1 expression was lowly detected in cerebellum-like structures indicating that although generatively homologous, the cerebellum and cerebellum-like structures do not share a complete overlap of common expression. Because of the little skate's important phylogenetic placement, performing molecular methodologies to assay targeted gene expression and determine protein localization in the hindbrain can be valuable for our understanding of cerebellar evolution and comparative neural development.
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PMID:Inositol 1,4,5-triphosphate receptor is selectively expressed in cerebellum but not cerebellum-like structures of the elasmobranch fish, Leucoraja erinacea. 3077 73