Five questions on improving diversity, equity and inclusion in UK bioscience research or "How can UK bioscience be changed so that those from marginalised groups can thrive?"

Diversity, equity, and inclusion play pivotal roles in advancing science and innovation by fostering a rich and supportive environment that benefits both individuals and society. UK bioscience research units are still on a journey towards being inclusive, and existing research on effecting changes in diversity, equity, and inclusion has yet to make an impact at the scale needed to transform the sector, leaving many to wonder How can UK bioscience be changed so that those from marginalised groups can thrive? This paper considers some of the questions that arise in addressing this, discusses what we already know and what we do not, and in doing so outlines a research agenda that aims to find out what works to effect diversity, equity and inclusion in UK bioscience.

Maculopathy and adult-onset ataxia in patients with biallelic MFSD8 variants.

BACKGROUND: Biallelic variants in the major facilitator superfamily domain containing 8 gene (MFSD8) are associated with distinct clinical presentations that range from typical late-infantile neuronal ceroid lipofuscinosis type 7 (CLN7 disease) to isolated adult-onset retinal dystrophy. Classic late-infantile CLN7 disease is a severe, rare neurological disorder with an age of onset typically between 2 and 6 years, presenting with seizures and/or cognitive regression. Its clinical course is progressive, leading to premature death, and often includes visual loss due to severe retinal dystrophy. In rare cases, pathogenic variants in MFSD8 can be associated with isolated non-syndromic macular dystrophy with variable age at onset, in which the disease process predominantly or exclusively affects the cones of the macula and where there are no neurological or neuropsychiatric manifestations. METHODS: Here we present longitudinal studies on four adult-onset patients who were biallelic for four MFSD8 variants. RESULTS: Two unrelated patients who presented with adult-onset ataxia and had macular dystrophy on examination were homozygous for a novel variant in MFSD8 NM_152778.4: c.935T>C p.(Ile312Thr). Two other patients presented in adulthood with visual symptoms, and one of these developed mild to moderate cerebellar ataxia years after the onset of visual symptoms. CONCLUSIONS: Our observations expand the knowledge on biallelic pathogenic MFSD8 variants and confirm that these are associated with a spectrum of more heterogeneous clinical phenotypes. In MFSD8-related disease, adult-onset recessive ataxia can be the presenting manifestation or may occur in combination with retinal dystrophy.

Characterization of two human induced pluripotent stem cell lines derived from Batten disease patient fibroblasts harbouring CLN5 mutations.

The neuronal ceroid lipofuscinoses (NCLs) are a group of common inherited neurodegenerative disorders of childhood. All forms of NCLs are life-limiting with no curative treatments. Most of the 13 NCL genes encode proteins residing in endolysosomal pathways, such as CLN5, a potential lysosomal enzyme. Two induced pluripotent stem cell lines (hiPSCs) were generated from skin fibroblasts of CLN5 disease patients via non-integrating Sendai virus reprogramming. They demonstrate typical stem cell morphology, express pluripotency markers, exhibit trilineage differentiation potential and also successfully differentiate into neurons. These hiPSCs represent a potential resource to model CLN5 disease in a human context and investigate potential therapies.