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.

Differences in the topographic profiles of retinal thickening in eyes with and without serous macular detachment associated with diabetic macular oedema.

PURPOSE: To investigate if cases of diabetic macular oedema (DMO) associated with serous macular detachment (SMD) have a different topographic profile of retinal thickening compared with DMO cases not associated with SMD. METHODS: Optical coherence tomography scans of 152 eyes from 152 patients with centre-involving DMO and central subfield thickness >350 µm were identified. Measurements were taken of the neural retina at the highest point of thickening within the central subfield (H) and lateral extent of retina thicker than 350 µm (W). Group means were compared between eyes with SMD and eyes without SMD. RESULTS: SMD was present in 55 eyes (36%). H was lower in eyes with SMD than in eyes without SMD (396 µm vs 550 µm, p<0.001) while W was higher in eyes with SMD compared with eyes without SMD (4.74 mm vs 4.18 mm, p=0.011). CONCLUSIONS: There were distinct differences in topographical profiles of retinal thickening between eyes with SMD and eyes without SMD. These findings suggest a possible mechanical basis for the pathogenesis of SMD in DMO.

Willingness and attitudes of the general public towards the involvement of medical students in their healthcare.

OBJECTIVES: To determine if patients allow medical students to perform less invasive procedures compared to more invasive procedures, and how this is related to patient demographics and previous experience with medical students. METHODS: A cross-sectional survey was conducted in six areas of Birmingham, UK. All members of the general public over the age of 18 were eligible, excluding non-English speaking people and those with cognitive impairments. Respondents were asked to rank their willingness for medical students to perform history taking/examinations and clinical procedures of varying degrees of invasiveness. RESULTS: We received a total of 293 responses. For both history taking/examinations and clinical procedures, people were more willing to allow medical students to perform less invasive procedures rather than more invasive procedures. White and older people were more willing to allow all history taking/examinations procedures; additionally, women were more willing to allow history taking. White, female, and older participants were more willing to allow blood pressure measurement; whilst older people and those with previous experience were more willing to allow venepuncture. No significant associations were found for intubation. CONCLUSIONS: The public is less willing for medical students to perform more invasive procedures. This may severely limit opportunities to attain clinical competencies.