From 1995, Dr Shaw Smith undertook a Wellcome Trust Clinical Training Fellowship under the supervision of Dr Julian Walters in the Department of Medicine, Hammersmith Hospital (then the Royal Postgraduate Medical School) and Dr David Bentley at the Wellcome Trust Sanger Institute (then Sanger Centre). The research focused on the identification of differentially expressed transcripts in the small intestine and was successful in novel gene identification as well as methodological development.  Dr Shaw-Smith was awarded a Ph.D. for this work in 1999.

Following completion of his Ph.D., Dr Shaw Smith worked for around a year in the X chromosome mapping group at the Sanger Centre under the direction of Dr Mark Ross. This work used the technique of DNA fingerprinting to identify large insert bacterial clones suitable for generating a backbone for X chromosome sequencing. The X chromosome sequence was published in 2005.

In 2002, in collaboration with Dr Nigel Carter and under the supervision of Prof Martin Bobrow, Dr Shaw Smith returned to the Sanger Institute to develop the technique of array-based comparative genomic hybridisation for use in diagnosis of children with constitutional chromosome abnormalities. This work was successful and resulted in a publication in the Journal of Medical Genetics in 2004, which has been cited over 500 times. The work was reproduced by other research groups and subsequently adopted by clinical laboratories around the world. The technique was formally adopted as a replacement for the then laboratory standard, G-banded karyotyping, in 2010. Application of this technique to children with learning disability and congenital malformations led to the identification of new, previously undescribed, syndromes. The first such syndrome to be identified by this method, the 17q21.3 microdeletion syndrome, was published in 2006 by the Sanger team and also by teams working in the United States and the Netherlands. This work was the subject of a News and Views article and editorial in the issue of Nature Genetics in which it was published in 2006, and was highlighted on the front cover of the journal.

In 2005, Dr Shaw Smith set up the Genetics of Oesophageal Atresia project, with start-up funding from the UK support group for this malformation, TOFS. Subsequently, Dr Shaw Smith was awarded a Wellcome Trust Intermediate Clinical Fellowship to continue this work, again based at the Sanger Institute. The work, carried out between 2006 and 2010, resulted in the identification of the role of FOXF1 in congenital malformations of the gastrointestinal tract and other organs (Stankiewicz et al, 2010).

In 2010, Dr Shaw Smith moved to Exeter in order to take up a post jointly funded by the Clinical Genetics Department and the University of Exeter. He has continued his interest in the genetics of gastro-intestinal malformations, and of heritable renal disorders.

Selected publications

Familial interstital nephritis:  42 years from case series to genetic diagnosis.  Clissold RL, Bingham C, Shaw-Smith C.  Clin Nephrol. 2019 Jun;91(6):386-388. doi: 10.5414/CN109654. PMID: 30686289

Further delineation of Malan syndrome.  Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K, Acero IH, Alkuraya FS, Arias P, Bernardini L, Bijlsma EK, Cole T, Coubes C, Dapia I, Davies S, Di Donato N, Elcioglu NH, Fahrner JA, Foster A, González NG, Huber I, Iascone M, Kaiser AS, Kamath A, Liebelt J, Lynch SA, Maas SM, Mammì C, Mathijssen IB, McKee S, Menke LA, Mirzaa GM, Montgomery T, Neubauer D, Neumann TE, Pintomalli L, Pisanti MA, Plomp AS, Price S, Salter C, Santos-Simarro F, Sarda P, Segovia M, Shaw-Smith C, Smithson S, Suri M, Valdez RM, Van Haeringen A, Van Hagen JM, Zollino M, Lapunzina P, Thakker RV, Zenker M, Hennekam RC.  Hum Mutat. 2018 Jun 13. PMID: 29897170

Discovery of a novel dominant mutation in the REN gene after forty years of renal disease: a case report. Clissold RL, Clarke HC, Spasic-Boskovic O, Brugger K, Abbs S, Bingham C, Shaw-Smith C.  BMC Nephrol. 2017 Jul 12;18(1):234. doi: 10.1186/s12882-017-0631-5.  PMID: 28701203

Prevalence and architecture of de novo mutations in developmental disorders.  Deciphering Developmental Disorders Study. Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.

Isolated Pancreatic Aplasia Due to a Hypomorphic PTF1A Mutation. Houghton JA, Swift GH, Shaw-Smith C, Flanagan SE, de Franco E, Caswell R, Hussain K, Mohamed S, Abdulrasoul M, Hattersley AT, MacDonald RJ, Ellard S. Diabetes. 2016 Sep;65(9):2810-5. doi: 10.2337/db15-1666. Epub 2016 Jun 9. PMID: 27284104

Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.  Weedon MN, Cebola I, Patch AM, Flanagan SE, De Franco E, Caswell R, Rodríguez-Seguí SA,Shaw-Smith C, Cho CH, Lango Allen H, Houghton JA, Roth CL, Chen R, Hussain K, Marsh P, Vallier L, Murray A; International Pancreatic Agenesis Consortium, Ellard S, Ferrer J, Hattersley AT. Nat Genet. 2014 Jan;46(1):61-4. doi: 10.1038/ng.2826. Epub 2013 Nov 10.  PMID: 24212882

GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency.  De Franco E, Shaw-Smith C, Flanagan SE, Shepherd MH; International NDM Consortium, Hattersley AT, Ellard S.  Diabetes. 2013 Mar;62(3):993-7. doi: 10.2337/db12-0885. Epub 2012 Dec 6. PMID: 23223019 

GATA6 haploinsufficiency causes pancreatic agenesis in humans.  Lango Allen H, Flanagan SE, Shaw-Smith C, De Franco E, Akerman I, Caswell R; International Pancreatic Agenesis Consortium, Ferrer J, Hattersley AT, Ellard S.  Nat Genet. 2011 Dec 11;44(1):20-2. doi: 10.1038/ng.1035. PMID: 22158542

High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia.  Nik-Zainal S, Strick R, Storer M, Huang N, Rad R, Willatt L, Fitzgerald T, Martin V, Sandford R, Carter NP, Janecke AR, Renner SP, Oppelt PG, Oppelt P, Schulze C, Brucker S, Hurles M, Beckmann MW, Strissel PL, Shaw-Smith C. J Med Genet. 2011 Mar;48(3):197-204. doi: 10.1136/jmg.2010.082412. Epub 2011 Jan 28. PMID: 21278390

Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, Ou Z, Wiszniewska J, Driscoll DJ, Maisenbacher MK, Bolivar J, Bauer M, Zackai EH, McDonald-McGinn D, Nowaczyk MM, Murray M, Hustead V, Mascotti K, Schultz R, Hallam L, McRae D, Nicholson AG, Newbury R, Durham-O’Donnell J, Knight G, Kini U, Shaikh TH, Martin V, Tyreman M, Simonic I, Willatt L, Paterson J, Mehta S, Rajan D, Fitzgerald T, Gribble S, Prigmore E, Patel A, Shaffer LG, Carter NP, Cheung SW, Langston C,Shaw-Smith C. Am J Hum Genet. 2009 Jun;84(6):780-91. doi: 10.1016/j.ajhg.2009.05.005. Epub 2009 Jun 4. Erratum in: Am J Hum Genet. 2009 Oct;85(4):537. multiple author names added. PMID: 19500772

Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, Saugier-Veber P, Pfundt R, Vissers LE, Destrée A, Grisart B, Rooms L, Van der Aa N, Field M, Hackett A, Bell K, Nowaczyk MJ, Mancini GM, Poddighe PJ, Schwartz CE, Rossi E, De Gregori M, Antonacci-Fulton LL, McLellan MD 2nd, Garrett JM, Wiechert MA, Miner TL, Crosby S, Ciccone R, Willatt L, Rauch A, Zenker M, Aradhya S, Manning MA, Strom TM, Wagenstaller J, Krepischi-Santos AC, Vianna-Morgante AM, Rosenberg C, Price SM, Stewart H, Shaw-Smith C, Brunner HG, Wilkie AO, Veltman JA, Zuffardi O, Eichler EE, de Vries BB. J Med Genet. 2008 Nov;45(11):710-20. doi: 10.1136/jmg.2008.058701. Epub 2008 Jul 15. Erratum in: J Med Genet. 2009 Aug;46(8):576. PMID: 18628315

Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos AC, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP. Nat Genet. 2006 Sep;38(9):1032-7. Epub 2006 Aug 13. PMID: 16906163

Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL association: review of genetics and epidemiology. Shaw-Smith C. J Med Genet. 2006 Jul;43(7):545-54. Epub 2005 Nov 18. Review. PMID: 16299066

Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features.  Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L, Fiegler H, Firth H, Sanlaville D, Winter R, Colleaux L, Bobrow M, Carter NP. J Med Genet. 2004 Apr;41(4):241-8. PMID: 15060094

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Coffey AJ, Brooksbank RA, Brandau O, Oohashi T, Howell GR, Bye JM, Cahn AP, Durham J, Heath P, Wray P, Pavitt R, Wilkinson J, Leversha M, Huckle E, Shaw-Smith CJ, Dunham A, Rhodes S, Schuster V, Porta G, Yin L, Serafini P, Sylla B, Zollo M, Franco B, Bolino A, Seri M, Lanyi A, Davis JR, Webster D, Harris A, Lenoir G, de St Basile G, Jones A, Behloradsky BH, Achatz H, Murken J, Fassler R, Sumegi J, Romeo G, Vaudin M, Ross MT, Meindl A, Bentley DR. Nat Genet. 1998 Oct;20(2):129-35. PMID: 9771704

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