Jenny Taylor, Genomic Medicine, University of Oxford

Dianne Newbury, Faculty of Lifesciences and Health, Oxford Brookes University

Arjune Sen, Nuffield Department of Clinical Neurosciences, University of Oxford

Laurent Servais, Department of Paediatrics, University of Oxford

Christoffer Nellaker, Oxford Big Data Institute, University of Oxford

Taroh Kinoshita, RIDM, Osaka University, Japan

Yoshiko Murakami, RIDM, Osaka University, Japan

Tyler Pierson, Cedars Sinai, USA

Taisiia Sazonova

Kuki Davey

Eleanor Hogg

Ishita Bhatnagar

Kate Wilson

Lucy Loong

Agostina Tardivo

Lara Hawkes

Renata Oliviera

Rita Ibitoye

Kini: Personalised therapeutic interventions in genetic epilepsies: clinical and molecular approaches — Radcliffe Department of Medicine (ox.ac.uk)

My research is inspired by a need to deliver patient benefit through enhanced diagnostics, improved understanding of the genetic basis of rare disease (particularly neurodevelopmental disorders, epilepsy and congenital malformations including structural brain abnormalities and orofacial clefting) and thereby formulating a path to driving targeted therapy and personalised medicine. We used advanced genetic technologies which enabled the discovery of several novel genes causing human disease such as PI4KA, HNRNPK, SOX11 and numerous GPI-Anchor Pathway genes including PGAP3, PIGY and PIGH. More extensive work on the GPI-AP has led to better understanding of the genotype-phenotype correlations and phenotypic spectrum in this pathway. My research has actively contributed to the characterisation of several new neurodevelopmental disorders caused by newly described genes, for example, USP9X, DDX3X, GATAD2B, SATB1.

My group has also been studying the molecular networks involved in orofacial clefting and speech disorders by examining data available from large-scale genetics studies such as Deciphering Developmental Disorders (DDD). Following on from this we have embarked upon a journey of exploring new neurodevelopmental disorders linked to the SATB pathway.

I also lead the Genseize project which is a transformation project (funded by NHSE via Central and South Genomic Medicine Service Alliance) which aims at offering sophisticated genetic testing to all patients with primary epilepsy. This project is an exemplar of engagement of primary care, community care and patient groups in delivering equity of access to genomic testing in the underserved populations.

Understanding the natural history of rare diseases is important in developing objective measurable outcomes for therapeutic trials. I am the Principal Investigator for the NatHis Angelman Syndrome study UK (funded by the support group charity FAST UK). This study is being carried out in readiness for clinical trials.

den Hoed J, de Boer E, 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 7

Pagnamenta AT, Murakami Y, 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.

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

Piard J, Hawkes L, et al. The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature. Genet Med. 2019 Jun;21(6):1308-1318.

Adab N, Kini U, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2004 Nov;75(11):1575-83

Expanding the phenotype of ASXL3-related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3.

Schirwani S, Albaba S, Carere DA, Guillen Sacoto MJ, Milan Zamora F, Si Y, Rabin R, Pappas J, Renaud DL, Hauser N, Reid E, Blanchet P, Foulds N, Dixit A, Fisher R, Armstrong R, Isidor B, Cogne B, Schrier Vergano S, Demirdas S, Dykzeul N, Cohen JS, Grand K, Morel D, Slavotinek A, Albassam HF, Naik S, Dean J, Ragge N, Cinzia C, Tedesco MG, Harrison RE, Bouman A, Palen E, Challman TD, Willemsen MH, Vogt J, Cunniff C, Bergstrom K, Walia JS, Bruel AL, Kini U, Alkuraya FS, Slegesky V, Meeks N, Girotto P, Johnson D; DDD Study, Newbury-Ecob R, Ockeloen CW, Prontera P, Lynch SA, Li D, Graham JM Jr, Balasubramanian M.Am J Med Genet A. 2021 Nov;185(11):3446-3458

 PIGG variant pathogenicity assessment reveals characteristic features within 19 families.

Tremblay-Laganière C, Maroofian R, Nguyen TTM, Karimiani EG, Kirmani S, Akbar F, Ibrahim S, Afroze B, Doosti M, Ashrafzadeh F, Babaei M, Efthymiou S, Christoforou M, Sultan T, Ladda RL, McLaughlin HM, Truty R, Mahida S, Cohen JS, Baranano K, Ismail FY, Patel MS, Lehman A, Edmondson AC, Nagy A, Walker MA, Mercimek-Andrews S, Maki Y, Sachdev R, Macintosh R, Palmer EE, Mancini GMS, Barakat TS, Steinfeld R, Rüsch CT, Stettner GM, Wagner M, Wortmann SB, Kini U, Brady AF, Stals KL, Ismayilova N, Ellard S, Bernardo D, Nugent K, McLean SD, Antonarakis SE, Houlden H, Kinoshita T, Campeau PM, Murakami Y.Genet Med. 2021 Oct;23(10):1873-1881

 De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Gregor A, Meerbrei T, Gerstner T, Toutain A, Lynch SA, Stals K, Maxton C, Lemke JR, Bernat JA, Bombei HM, Foulds N, Hunt D, Kuechler A, Beygo J, Stöbe P, Bouman A, Palomares-Bralo M, Santos-Simarro F, Garcia-Minaur S, Pacio-Miguez M, Popp B, Vasileiou G, Hebebrand M, Reis A, Schuhmann S, Krumbiegel M, Brown NJ, Sparber P, Melikyan L, Bessonova L, Cherevatova T, Sharkov A, Shcherbakova N, Dabir T, Kini U, Schwaibold EMC, Haack TB, Bertoli M, Hoffjan S, Falb R, Shinawi M, Sticht H, Zweier C.Hum Mol Genet. 2021 Sep 9:ddab265.

 Identification of LAMA1 mutations ends diagnostic odyssey and has prognostic implications for patients with presumed Joubert syndrome.

Powell L, Olinger E, Wedderburn S, Ramakumaran VS, Kini U, Clayton-Smith J, Ramsden SC, Rice SJ, Barroso-Gil M, Wilson I, Cowley L, Johnson S, Harris E, Montgomery T, Bertoli M; Genomics England Research Consortium, Boltshauser E, Sayer JA.Brain Commun. 2021 Jul 16;3(3):fcab163

 Lockdown lessons: The virtual cleft multidisciplinary clinic. Armstrong ACG, Sibley J, Phippen G, Popat S, Pal R, Kini U, Hotton M, Kidner G, Thorburn TG, Swan MC.J Plast Reconstr Aesthet Surg. 2021 Aug;74(8):1931-1971