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  • Usha Kini

Usha_Kini Image.jpg


Speech and language are quintessential Human traits which usually develop with relative ease. Disruption of speech development is relatively rare and is considered a marker of severe neurodevelopmental disorder, yet we have little understanding of the molecular mechanisms underlying this ability. We have recently identified a new neurodevelopmental syndrome caused by disruption of the SATB1 gene. Using genomic data from the Deciphering Developmental Disorders (DDD) dataset, which includes over 13,000 individuals affected by severe developmental conditions, we have identified 32 patients affected by SATB1-related syndrome (1). Ninety percent of patients assessed had severe speech and language difficulties and 35% were completely nonverbal. Other common features of the syndrome include intellectual disability, low muscle tone and muscle weakness. We have shown that the identified variants have a functional effect on the cellular function of the SATB1 protein. SATB1 is known to interacts directly with other neurodevelopmental genes, including FOXP1and SATB2, which act as transcriptional regulators and chromatin remodelling agents. These exciting preliminary data suggest the existence of a specific gene network involved in speech and language development.


The focus of the Kini group ( ) is translational research aimed at the diagnosis and treatment of rare neurodevelopmental disorders. This is achieved by gene discovery and a deeper understanding of molecular networks involved in the disorders. In this project, we will follow a bioinformatic approach to identify SATB1-interacting genes and assess their likely association with the SATB-network, using sequence data from the DDD cohort. Objective 1: identify individuals in the DDD cohort who carry rare, deleterious variants in genes known to interact with SATB1 or SATB2. Objective 2: catalogue the clinical symptoms of individuals carrying pathogenic variants in SATB-related genes. Objective 3: carry out functional experiments to determine the pathogenicity of the novel variants/genes identified. Objective 4: screen additional genomic datasets to identify further individuals carrying pathogenic variants in key SATB-related genes identified from objectives 1 and 2. This will allow us to further delineate associated trajectories for affected individuals and provide a clearer clinical picture for these disorders. 

The use of a network approach will permit a fuller understanding of the relative contributions of related genes to speech and language. Once key genes are identified, this may lead to the creation of focused support groups for families affected with these rare disorders (for example, see  

This project will provide the student with opportunities to:

- become familiar with the manipulation of large genetic/genomic datasets

- develop bioinformatics skills 

- identify and describe new neurodevelopmental syndromes through gene discovery

- apply known assays and develop new experimental strategies to establish pathogenicity of genetic variants

- understand genetic mechanisms of disease 

- understand the importance of deep phenotyping

- collaborate with other researchers around the world exchange data and identify new patients in larger cohorts

- collaboratively develop human disease models and disease biomarkers, wherever possible 


Training Opportunities

This is the one of the few groups at the University of Oxford studying rare neurodevelopmental disorders in patients and using the ‘bench to bedside’ approach both in ‘forward’ and ‘reverse’. The group has vast experience in exploring poorly studied molecular networks to describe novel disease-causing genes and the related new neurodevelopmental syndromes (for example, the GPI-AP has now been well-studied with several novel genes causing human disease described) (2).  There is also an interest in studying the natural history of these rare diseases and their genotype-phenotype correlation for direct patient benefit. Development of biomarkers to monitor outcome of therapy is another focus, particularly with personalised medicine being on the national agenda for management of patients.

This group works well with collaborators across continents, as is needed to make any research pertaining to rare diseases meaningful. There are plans to consider using newer in- vitro dynamic human organ models to study not only the effects of the genetic variants on brain development but also the effects of therapy.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.


(1)   den Hoed J, et al., Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction. Am J Hum Genet. 2021 Feb 4;108(2):346-356

Pagnamenta AT, et al., Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders. Eur J Hum Genet. 2017 Jun;25(6):669-679.


den Hoed J, et al., Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction. Am J Hum Genet. 2021 Feb 4;108(2):346-356

Shieh C, et al., GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder. Genet Med. 2020 May;22(5):878-888

Bayat A, et al., PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor: description of 13 novel patients and expansion of the clinical characteristics. Genet Med. 2019 Oct;21(10):2216-2223

Piard J, et al. The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature. Genet Med. 2018 Oct 25

Pagnamenta AT, et al., Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders. Eur J Hum Genet. 2017 Jun;25(6):669-679

Bengani H, et al., Clinical and molecular consequences of disease-associated de novo mutations in SATB2. Genet Med. 2017