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BACKGROUND AND OBJECTIVES: To expand the clinical knowledge of GPAA1-related glycosylphosphatidylinositol (GPI) deficiency. METHODS: An international case series of 7 patients with biallelic GPAA1 variants were identified. Clinical, biochemical, and neuroimaging data were collected for comparison. Where possible, GPI-anchored proteins were assessed using flow cytometry. RESULTS: Ten novel variants were identified in 7 patients. Flow cytometry samples of 3 available patients confirmed deficiency of several GPI-anchored proteins on leukocytes. Extensive phenotypic information was available for each patient. The majority experienced developmental delay, seizures, and hypotonia. Neuroimaging revealed cerebellar anomalies in the majority of the patients. Alkaline phosphatase was within the normal range in 5 individuals and low in 1 individual, as has been noted in other transamidase defects. We notably describe individuals either less affected or older than the ones published previously. DISCUSSION: Clinical features of the cases reported broaden the spectrum of the known phenotype of GPAA1-related GPI deficiency, while outlining the importance of using functional studies such as flow cytometry to aid in variant classification.

Activating variants in the PIK3CA gene cause a heterogeneous spectrum of disorders that involve congenital or early‐onset segmental/focal overgrowth, now referred to as PIK3CA‐related overgrowth spectrum (PROS). Historically, the clinical diagnoses of patients with PROS included a range of distinct syndromes, including CLOVES syndrome, dysplastic megalencephaly, hemimegalencephaly, focal cortical dysplasia, Klippel–Trenaunay syndrome, CLAPO syndrome, fibroadipose hyperplasia or overgrowth, hemihyperplasia multiple lipomatosis, and megalencephaly capillary malformation‐polymicrogyria (MCAP) syndrome. MCAP is a sporadic overgrowth disorder that exhibits core features of progressive megalencephaly, vascular malformations, distal limb malformations, cortical brain malformations, and connective tissue dysplasia. In 2012, our research group contributed to the identification of predominantly mosaic, gain‐of‐function variants in PIK3CA as an underlying genetic cause of the syndrome. Mosaic variants are technically more difficult to detect and require implementation of more sensitive sequencing technologies and less stringent variant calling algorithms. In this study, we demonstrated the utility of deep sequencing using the Illumina TruSight Oncology 500 (TSO500) sequencing panel in identifying variants with low allele fractions in a series of patients with PROS and suspected mosaicism: pathogenic, mosaic PIK3CA variants were identified in all 13 individuals, including 6 positive controls. This study highlights the importance of screening for low‐level mosaic variants in PROS patients. The use of targeted panels with deep sequencing in clinical genetic testing laboratories would improve diagnostic yield and accuracy within this patient population. [ABSTRACT FROM AUTHOR]

The Open University (OU) is the UK's largest distance education provider and has a large and growing disabled student population. Disabled user support presents particular challenges for an online library service in the distance learning environment. The OU introduced guidelines for working with non-OU--authored content (external content) in 2011 which fundamentally altered the focus of library support from on-demand conversions to preemptive identification--and where necessary, conversion--of essential content. This case study describes Library Services' learning journey through its support for one particular module with lots of external content, the resultant benefits to its support services and considers areas for future development.

This article reports on targeting distance learners using electronic messaging. Higher education and Open University policy has been moving towards e-learning and independent study. Open University courses increasingly require students to develop skills and to use online resources to research their topics.