We have a long history of identifying the underlying genetic cause of distinct genetic syndromes such as Cohen Syndrome, Say-Barber-Biesecker syndrome, Ochoa syndrome, Burn-McKeown syndrome, POU3F2 deletion syndrome and Fillipi syndrome. We also work collaboratively with other centres;for example, team members have enrolled over 900 patients into the UK Deciphering Developmental Disorders (DDD) Study which has led to the recognition and further delineation of new syndromes such as PURA syndrome and DYRK1A syndrome. We have also recruited over a 1000 developmental disorder patients so far into the UK 100,000 Genomes England Study.

We have undertaken studies to understand the role of genes discovered in both health and disease through research at The University of Manchester and in collaboration with world-wide colleagues. Examples include work on MEK/ERK pathway defects in Kabuki syndrome and effects of heparanase 2 on neural development on Ochoa syndrome. We have also been involved in a large body of work delineating the effects of in utero antiepileptic drug exposure on physical and neurodevelopment, particularly concerning the Fetal Valproate Syndrome.

Several team members have developed expertise in diagnosing and managing specific disorders and through their clinical research have assembled large clinical cohorts for study. These disorders include type I interferonopathies, Williams syndrome, Cohen syndrome, Neurofibromatosis type 1, Fetal Valproate syndrome, Kabuki syndrome, Coffin-Siris syndrome, CHARGE syndrome, Angelman syndrome, and the conditions called “Rasopathies” ie Noonan syndrome and its variants, Costello syndrome and Cardio-facio-cutaneous syndrome. This expertise has enabled us to contribute high quality clinical information to many papers describing the natural history of these rare disorders and to provide appropriate information for patients and families.

We have the longstanding aim of improving healthcare for patients with rare diseases. To this end, we have produced care pathways and guidelines for a number of rare conditions by consultation with other experts and affected patients and their families. The laboratory scientists in the team have introduced new and innovative testing for more rapid and effective diagnosis of rare diseases. We regularly recruit patients with rare disease into clinical trials, with team members acting as Principal Investigators on observational and interventional clinical studies.

We host a large number of undergraduate and post-graduate students within our team as they undertake research studies on Developmental Disorders leading to degree qualifications. In addition, we accept visiting researchers for shorter research attachments. We provide significant input to the undergraduate programme by supervising student research projects (APEPS) and introduce school age students to research through a number of initiatives. Through ERN-ITHACA, the newly established European Reference Network on congenital malformations and intellectual disability, we plan to offer short research attachments to our colleagues throughout Europe. Members of our team sit on grant awarding bodies and regularly review medical literature.

We host a two-yearly Manchester International Dysmorphology Meeting, renowned for it’s high quality, where research findings in the field are shared. We participate in a number of patient support group meetings, giving presentations to update lay groups on research findings. We are major contributors of articles to peer-reviewed journals in the field of developmental disorders with in excess of 75 articles each year from members of our team. The Clinical Dysmorphology journal is edited by our departmental team and provides a platform for trainees in particular to begin to contribute to medical literature.

MCGM Clinical & Research

MCGM Laboratory

International Costello syndrome support group (UK)
Costello Syndrome Family Support Network (USA)
Noonan Syndrome Association UK
Williams’ syndrome foundation UK
Rett syndrome association UK
Cohen Syndrome Support Group UK
The Fanconi Hope Charitable Trust

• Great Ormond St Hospital
• University of Cambridge
• University of Southampton

• Action Medical Research
• National Institute of Health Research

National Collaborative studies;

• 100,000 Genomes project
• Deciphering Developmental Disorders Study Manchester arm of Wellcome Trust/NIHR National DDD study
• DECIPHER Study; Database of Chromosomal imbalance and phenotype in humans using Ensembl resources.
• BINGO study; Neuroanatomical, cognitive and behavioural phenotypes in intellectual disability of genetic origin.
• PAGE (Prenatal Assessment of Genomes and Exomes) project; New Methods of Detecting Problems in Pregnancy
• IDFOW; Imprinting Disorders (Finding Out Why) Study
• IMAGINE ID; Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment
• NIPSIGEN Clinical translation of NIPD for single gene disorders; Manchester arm of national study on non-invasive prenatal testing
• ISO study. Isolated segmental Overgrowth. Manchester centre of UK multicentre-study for PIK3CA related disorders

MCGM led studies;

• Manchester Gene Identification Consortium (MAGIC) Study
• Understanding the disorders of the RAS-MAPK pathway.
• A prospective natural history study to enhance understanding of the phenotypes associated with a type I interferonopathies
• Understanding the role of U5 snRNP gene mutation in pre-messenger RNA splicing and craniofacial development. BBSRC funded

1. Garg S, Brooks A, Burns A, Burkitt-Wright E, Kerr B, Huson S, Emsley R, Green J. Autism Spectrum Disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway. Dev Med Child Neurol 2017; 59(5):544-549.
2. Deciphering Developmental Disorders Study Collaborators (302). Prevalence and architecture of de novo mutations in developmental disorders. Nature 2017; 542(7642):433-438.
3. Faily S, Perveen R, Urquhart J, Chandler K, Clayton-Smith J. Confirmation that mutations in DDX59 cause an autosomal recessive form of oral-facial-digital syndrome: Further delineation of the DDX59 phenotype in two new families. Eur J Med Genet. 2017; July 12, epub ahead of print
4. Balasubramanian M, Willoughby J, Fry AE, Weber A, Firth HV, Deshpande C, Berg JN, Chandler K, Metcalfe KA, Lam W, Pilz DT, Tomkins S. Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature. J Med Genet. 2017; 54(8):537-543.
5. Reuter MS, Riess A, Moog U, Briggs TA, Chandler KE, Rauch A, Stampfer M, Steindl K, Gläser D, Joset P; DDD Study, Krumbiegel M, Rabe H, Schulte-Mattler U, Bauer P, Beck-Wödl S, Kohlhase J, Reis A, Zweier C. FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum. J Med Genet. 2017; 54(1):64-72.
6. Symonds JD, Joss S, Metcalfe KA, Somarathi S, Cruden J, Devlin AM, Donaldson A, DiDonato N, Fitzpatrick D, Kaiser FJ, Lampe AK, Lees MM, McLellan A, Montgomery T, Mundada V, Nairn L, Sarkar A, Schallner J, Pozojevic J, Parenti I, Tan J, Turnpenny P, Whitehouse WP; DDD Study, Zuberi SM. Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases. Epilepsia. 2017;58(4):565-575.
7. Kasher PR, Schertz KE, Thomas M, Jackson A, Annunziata S, Ballesta-Martinez M, Campeau PM, Clayton PE, Eaton JL, Granata T, Guille’n-Navarro E, Hernando C, Laverriere CE, Liede’n A, Villa-Marco O, Mcentagart M, Nordgren A, Pantaleoni C, Pebrel-Richard C, Sarret C, Sciacca FL, Wright R, Kerr B, Glasgow E, Banka S. Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability. Am J Hum Genet 2016:98; 363-372.
8. Twigg SR, Hufnagel RB, Miller KA, Zhou Y, McGowan SJ, Taylor J, Craft J, Taylor JC, Santoro SL, Huang T, Hopkin RJ, Brady AF, Clayton-Smith J, Clericuzio CL, Grange DK, Groesser L, Hafner C, Horn D, Temple IK, Dobyns WB, Curry CJ, Jones MC, Wilkie AO. A recurrent mosaic mutation in SMO, encoding the hedgehog signaling transducer smoothened, is the major cause of Curry Jones syndrome. Am J Hum Genet. 2016 2;98(6):1256-65.
9. McEntagart M, Williamson KA, Rainger JK, Wheeler A, Seawright A, De Baere E, Verdin H, Bergendahl LT, Quigley A, Rainger J, Dixit A, Sarkar A, López Laso E, Sanchez-Carpintero R, Barrio J, Bitoun P, Prescott T, Riise R, McKee S, Cook J, McKie L, Ceulemans B, Meire F, Temple IK, Prieur F, Williams J, Clouston P, Németh AH, Banka S, Bengani H, Handley M, Freyer E, Ross A; DDD Study, van Heyningen V, Marsh JA, Elmslie F, FitzPatrick DR. A restricted repertoire of de novo mutations in ITPR1 cause Gillespie syndrome with evidence for dominant negative effect. Am J Hum Genet. 2016 5;98(5):981-92.
10. de Goede C, Yue WW, Yan G, Ariyaratnam S, Chandler KE, Downes L, Khan N, Mohan M, Lowe M, Banka S. Role of reverse phenotyping in interpretation of next generation sequencing data and a review of INPP5E related disorders. Eur J Paediatr Neurol. 2016 Mar;20(2):286-95.
11. Douzgou S, Pollalis YA, Vozikis A, Patrinos GP, Clayton-Smith J. Collaborative Crowdsourcing for the Diagnosis of Rare Genetic Syndromes: The DYSCERNE experience. Public Health Genomics. 2016; 19(1):19-24.
12. Urquhart J, Roberts R, de Silva D, Shalev S, Chervinsky E, Nampoothiri S, Sznajer Y, Revencu N, Gunasekera R, Suri M, Ellingford J, Williams S, Bhaskar S, Clayton-Smith J. Exploring the genetic basis of 3MC syndrome. Findings in 12 further families. Am J Med Genet A. 2016;170(5):1216-24.
13. Srour M, Caron V, Pearson T, Nielsen SB, Lévesque S, Delrue MA, Becker TA, Hamdan FF, Kibar Z, Sattler SG, Schneider MC, Bitoun P, Chassaing N, Rosenfeld JA, Xia F, Desai S, Roeder E, Kimonis V, Schneider A, Littlejohn RO, Douzgou S, Tremblay A, Michaud JL. Gain-Of-Function Mutations In RARB Cause Intellectual Disability With Progressive Motor Impairment. Hum Mutat. 2016;37(8):786-93.
14. Banka S, Lederer D, Benoit V, Jenkins E, Howard E, Bunstone S, Kerr B, McKee S, Lloyd IC, Shears D, Stewart H, White SM, Savarirayan R, Mancini GMS, Beysen D, Cohn RD, Grisart B, Maystadt I, Donnai D. Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2). Clin Genet 2015:87(3): 252-258.
15. Beleza-Meireles A, Hart R, Clayton-Smith J, Oliveira R, Reis CF, Venâncio M, Ramos F, Sá J, Ramos L, Cunha E, Pires LM, Carreira IM, Scholey R, Wright R, Urquhart JE, Briggs TA, Kerr B, Kingston H, Metcalfe K, Donnai D, Newman WG, Saraiva JM, Tassabehji M. Oculoauriculovertebral syndrome; clinical and molecular analysis of 51 patients. Eur J Med Genet. 2015 Sep;58(9):455-65.
16. Lennon L, Stuart HM, Bierzynska A, Randles MJ, Kerr B, Hillman KA, Batra G, Campbell J, Storey H, Flinter FA, Koziell A, Welsh GI, Saleem MA, Webb NA, Woolf AS. Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of renal disease Pediatr Nephrol 2015; 30(9):1459-65.
17. Baker GA, Bromley RL, Briggs M, Cheyne CP, Cohen MJ, García-Fiñana M, Gummery A, Kneen R, Loring DW, Mawer G, Meador KJ, Shallcross R, Clayton-Smith J; Liverpool and Manchester Neurodevelopment Group. IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology. 2015 Jan 27; 84(4):382-90.
18. Banka S, Cain SA, Carim S, Daly SB, Urquhart JE, Erdem G, Harris J, Bottomley M, Donnai D, Kerr B, Kingston H, Superti-Furga A, Unger S, Ennis H, Worthington J, Herrick AL, Merry CL, Yue WW, Kielty CM, Newman WG. Leri’s pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis. Ann Rheum Dis. 2015;74(6):1249-56.
19. Schneider M, Chandler K, Tischkowitz M, Meyer S. Fanconi anaemia: genetics, molecular biology, and cancer – implications for clinical management in children and adults. Clin Genet. 2015 Jul;88(1):13-24.
20. Wieczorek D, Newman WG, Wieland T, Berulava T, Kaffe M, Falkenstein D, Beetz C, Graf E, Schwarzmayr T, Douzgou S, Clayton-Smith J, Daly SB, Williams SG, Bhaskar SS, Urquhart JE, Anderson B, O’Sullivan J, Boute O, Gundlach J, Czeschik JC, van Essen AJ, Hazan F, Park S, Hing A, Kuechler A, Lohmann DR, Ludwig KU, Mangold E, Steenpaß L, Zeschnigk M, Lemke JR, Lourenco CM, Hehr U, Prott EC, Waldenberger M, Böhmer AC, Horsthemke B, O’Keefe RT, Meitinger T, Burn J, Lüdecke HJ, Strom TM. Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome. Am J Hum Genet. 2014; 95(6):698-707.