Medicine, Nursing and Allied Health Professions


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Dr Richard Caswell

Dr Richard Caswell

Associate Researcher

 01392 408506

 RILD Building 


University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

 Office hours:

My normal working days are Tuesday & Wednesday


I worked as a member of the Monogenic Diabetes group from June 2009 until August 2019, using high-throughput (‘Next Generation’) sequencing techniques for the discovery of novel causative genes and mutations in neonatal diabetes, hyperinsulinism and other diseases of pancreatic dysfunction. This work was carried out in close association with the Department of Molecular Genetics at the Royal Devon and Exeter NHS Foundation Trust, and having initially implemented these techniques for research studies, we were able to transfer these into the diagnostic setting, offering rapid, high-throughput testing not only for monogenic diabetes but for a wide range of inherited diseases. As well as continuing this work, I also developed high sensitivity methods for the non-invasive detection of specific diabetes mutations in pregnant mothers, which will help inform clinical care during and after pregnancy and reduce the risk of complications such as macrosomia (see 'Research'). This work brought together molecular genetic techniques with cutting-edge detection methods to allow delivery of truly personalized healthcare.

Prior to moving to Exeter, my experience as a protein biochemist gave me opportunities to collaborate with the Monogenic Diabetes and Molecular Genetics groups on interpreting the effects of novel missense variants. This work has continued and developed throughout my time in Exeter, and involves the analysis of protein sequence and structure using freely-available bioinformatics tools, to try to gain insights into the effect of variants on protein function. Since such effects are highly context-specific, this usually requires interpretation of potential molecular defects on a case-by-case basis, and this represents a challenge in the era of high-throughput sequencing and variant discovery. 

This work led to my transfer into a new role in September 2019 as a Healthcare Scientist with the Exeter Genomics Laboratory (formerly the Department of Molecular Genetics) at the RD&E NHS Foundation Trust, though I remain affiliated with the University of Exeter as an Associate Researcher. The focus of my new role is to develop further the use of protein structural analysis as a tool in the interpretation of missense variants, and our long-term goal is to bring such techniques into routine use in genetic diagnosis.


PhD (University of Wales, 1988)

BSc (Hons) (University of Wales, 1985)


Previous positions

  • 1997-2007: Lecturer, School of Biosciences, Cardiff University
  • 1991-1997: Postdoctoral Research Associate, School of Medicine, University of Cambridge
  • 1988-1991: Postdoctoral Research Fellow, Schools of Biochemistry and Chemical Engineering, University of Birmingham


Selected recent publications

Wakeling E, McEntagart M, Bruccoleri M, Shaw-Smith C, Stals KL, Wakeling M, Barnicoat A, Beesley C; DDD Study, Hanson-Kahn AK, Kukolich M, Stevenson DA, Campeau PM, Ellard S, Elsea SH, Yang XJ & Caswell RC. (2021). Missense substitutions at a conserved 14-3-3 binding site in HDAC4 cause a novel intellectual disability syndrome. HGG Advances 2:100015. PMID: 33537682.

Caswell RC, Snowsill T, Houghton JAL, Chakera AJ, Shepherd MH, Laver TW, Knight BA, Wright D, Hattersley AT & Ellard S. (2020). Non-invasive fetal genotyping by droplet digital PCR to identify maternally-inherited monogenic diabetes variants. Clinical Chemistry 66:958-965. PMID: 32533152.

Gunning AC, Strucinska K, Muñoz Oreja M, Parrish A, Caswell R et al. (2020). Recurrent de novo NAHR reciprocal duplications in the ATAD3 gene cluster cause a neurogenetic trait with perturbed cholesterol and mitochondrial metabolism. Am J Hum Genet. 106:272-279. PMID: 32004445.

Misra S, Hassanali N, Bennett AJ, Juszczak A, Caswell R et al. (2020). Homozygous hypomorphic HNF1A alleles are a novel cause of young-onset diabetes and result in sulphonylurea-sensitive diabetes. Diabetes Care. 43:909-912. PMID: 32001615.

De Franco E, Caswell R, Johnson MB, Wakeling MN, Zung A, Dũng VC et al. (2019). De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early onset diabetes and transient hepatic dysfunction. Diabetes. 69:477-483. PMID: 31882561.

Caswell RC, Owens MM, Gunning AC, Ellard S & Wright CF (2019). Using structural analysis in silico to assess the impact of missense variants in MEN1. J Endocrine Soc. 3:2258-2275. PMID: 31737856.

Rautengarten C, Quarrell OW, Stals K, Caswell R et al. (2019). A hypomorphic allele of SLC35D1 results in Schneckenbecken-like dysplasia. Hum Mol Genet. 28:3543-3551. PMID: 31423530.

Turnpenny PD, Wright MJ, Sloman M, Caswell R et al. (2018). Missense mutations of the Pro65 residue of PCGF2 cause a recognizable syndrome associated with craniofacial, neurological, cardiovascular, and skeletal features. Am J Hum Genet. 103:786-793. PMID: 30343942.

Iacovazzo D, Flanagan SE, Walker E, Quezado R, de Sousa Barros FA, Caswell R et al. (2018) MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Proc Natl Acad Sci U S A. 115:1027-1032. PMID: 29339498.

Stals KL, Wakeling M, Baptista J, Caswell R et al. (2017). Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing. Prenatal Diagnosis. 38:33-43. PMID: 29096039.

Hamilton MJ, Caswell RC, Canham N, Cole T et al. (2017). Heterozygous mutations affecting the protein kinase domain of CDK13 cause a syndromic form of developmental delay and intellectual disability. J Med Genet. 55:28-38. PMID: 29021403.

Elouej S, Beleza-Meireles A, Caswell R, Colclough K et al. (2017). Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL). Metabolism 71:213-225. PMID: 28521875.

Flanagan SE, Vairo F, Johnson MB, Caswell R, Laver TW, Lango Allen H, Hussain K & Ellard S (2017). A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatr Diabetes. 18:320-323. PMID: 28318089

Cabezas OR, Flanagan SE, Stanescu H, García-Martínez E, Caswell R et al. (2017). Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. J Am Soc Nephrol. 28:2529-2539. PMID: 28373276.

De Franco E, Caswell R, Houghton JA, Iotova V, Hattersley AT & Ellard S (2017). Analysis of cell-free fetal DNA for non-invasive prenatal diagnosis in a family with neonatal diabetes. Diabet Med. 34:582-585. PMID: 27477181.

Iacovazzo D, Caswell R, Bunce B, Jose S et al. (2016). Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun. 4:56. PMID: 27245663.

Laver TW, Caswell RC, Moore KA, Poschmann J, Johnson MB, Owens MM, Ellard S, Paszkiewicz KH & Weedon MN (2016). Pitfalls of haplotype phasing from amplicon-based long-read sequencing. Scientific Reports 6:21746. PMID: 26883533.

Sansbury FH, Kirel B, Caswell R, Allen Lango H, Flanagan SE, Hattersley AT, Ellard S, Shaw-Smith CJ (2015). Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus. European Journal of Human Genetics 23:1744-1748. PMID: 26264437.

Ellard S, Kivuva E, Turnpenny P, Stals K, Johnson M, Xie W, Caswell R & Lango Allen H (2015). An exome sequencing strategy to diagnose lethal autosomal recessive disorders. European Journal of Human Genetics 23:401-404. PMID: 24961629.

Flanagan SE, Haapaniemi E, Russell MA, Caswell R, Lango Allen H et al. (2014). Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nature Genetics 46:812-814. PMID: 25038750.

Hartill VL, Tysoe C, Manning N, Dobbie A, Santra S, Walter J, Caswell R, Koster J, Waterham H & Hobson E (2014). An unusual phenotype of X-linked developmental delay and extreme behavioral difficulties associated with a mutation in the EBP gene. American Journal of Medical Genetics A 164A:907-914. PMID: 24459067.

Lango Allen H, Caswell R, Xie W, Xu X, Wragg C, Turnpenny PD, Turner CLS, Weedon MN & Ellard S (2014). Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans. Journal of Medical Genetics 51:264-267. PMID: 24459211.

Ellard S, Lango Allen H, De Franco E, Flanagan SE, Hysenaj G, Colclough K, Houghton JAL, Shepherd M, Hattersley AT, Weedon MN & Caswell R (2013). Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 56:1958-1963. PMID: 23771172.

Weedon MN, Cebola I, Patch AM, Flanagan SE, De Franco E, Caswell R et al. (2014). Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. Nature Genetics 46:61-64. PMID: 24212882.

Weedon MN, Ellard S, Prindle MJ, Caswell R, Lango Allen H et al. (2013). An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nature Genetics 45:947-950. PMID: 23770608

Flanagan SE, Xie W, Caswell R, Damhuis A, Vianey-Saban C et al. (2013). Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation. American Journal of Human Genetics 92:131-136. PMID: 23273570.

Lango Allen H, Flanagan SE, Shaw-Smith S, De Franco E, Akerman I, Caswell R, International Pancreatic Agenesis Consortium, Ferrer J, Hattersley AT & Ellard S (2011). GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nature Genetics 44:20-22. PMID: 22158542.

Weedon MN, Hastings R, Caswell R, Xie W, Paszkiewicz K, Antoniadi T, Williams M, King C, Greenhalgh L, Newbury-Ecob R & Ellard S (2011). Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth Disease. American Journal of Human Genetics 89:308-312. PMID: 21820100.

Research group links


Research interests

Dr Caswell explains his research into non-invasive foetal DNA testing to predict pregnancies at risk of macrosomia in the video below, filmed at the Living Systems Institute Research Symposium in March 2016.


Supervision / Group

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