Missense mutation in the ITPR1 gene presenting with ataxic cerebral palsy: Description of an affected family and literature review

The inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene on chromosome 3 belongs to a family of genes encoding intracellular calcium channel proteins. Such channels are located primarily within the endoplasmic reticular membrane and release Ca2+, an intracellular messenger, which governs numerous intracellular and extracellular functions. We report a family with infantile-onset cerebellar ataxia with delayed motor development and intellectual disability caused by a heterozygous c.805C>T, p.Arg269Trp missense mutation in ITPR1. Both affected family members had postural tremor, hypotonia and dysarthria, but neither had pyramidal signs. Their neuroimaging revealed cerebellar atrophy. Several neurological conditions have been associated with ITPR1 mutations, such as spinocerebellar ataxia type 15 and Gillespie syndrome, and the phenotype may vary according to the location and type of mutations. Spinocerebellar ataxia type 15 is an autosomal dominant disorder, which causes late onset pure cerebellar ataxia. Gillespie syndrome is characterised by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia and cerebellar atrophy. In this report, we provide a detailed phenotypic description of a family with a missense mutation in ITPR1. This mutation has only been reported once before. We also provide a literature review of the various phenotypes associated with ITPR1 gene.