ASLX3-related disorder, also referred to as Bainbridge-Ropers syndrome, is characterised by developmental delay and intellectual disability caused by heterozygous, de novo pathogenic variants in ASXL3 (Additional Sex Combs-Like 3). Over the last decade, the Balasubramanian group has published most of the literature on this condition (Balasubramanian et al., 2017; Myers et al., 2018; Schirwani et al., 2019; Schirwani et al., 2021; Schirwani et al., 2023; Woods et al., 2024). We have also published a Genereview chapter on clinical diagnosis and management of the condition (Balasubramanian., 2020). Working with ‘Unique’ rare disease patient support group, we have published a patient guide for ASXL3. We now have a natural history study focused on longitudinal clinical data and sample collection for ASXL3. 

 HNRNPU-NDD is a neurodevelopmental disorder characterised by heterozygous, de novo, loss-of-function variants in HNRNPU. Patients with pathogenic variants in HNRNPU present with seizures, global developmental delay, early onset epilepsy, hypotonia, autistic features, and a variety of anatomical abnormalities and intellectual disability. The Balasubramanian group has published the largest HNRNPU patient cohort (Yates et al., 2017; Durkin et al., 2021; Taylor et al., 2022). We also published a Genereview chapter on clinical diagnosis and management of HNRNPU (Balasubramanian., 2022). We have an ongoing natural history study focused on longitudinal clinical data and sample collection for HNRNPU. Working with ‘Unique’ rare disease patient support group, we have published a patient guide for HNRNPU-related disorder. 

Novel gene discovery in OI and understanding disease mechanism for non-collagen OI genes. This involves mining genomics data for new gene discovery working alongside diagnostic colleagues from 100,000 Genomes project for which I lead the bone fragility domain as GeCIP lead and NHS whole genome sequencing. This has led to the identification of several novel OI genes which are being functionally assessed. An additional area is genes linking brain and bone disease such as Sodium Channelopathies, spermine synthase and SETD5 which I am exploring the causal link and why these disorders cause a bone phenotype. 

Mining genomics data for rare phenotypic presentations and discovering candidate genes for novel neurodevelopmental and congenital disorders and identifying additional international patients through interrogation of worldwide genomic datasets using GeneMatcher and Matchmaker exchange programmes; undertaking functional studies for publication of a novel genes.