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Hyperinsulinism

The Hyperinsulinism group's mission is to improve understanding of the genetics of congenital hyperinsulinism leading to improved patient care. The multi-disciplinary team consists of Molecular Geneticists, Data Scientists, Bioinformaticians, Clinical Scientists and Doctors who aim to:

  • Define the genetic aetiology of novel subtypes of congenital hyperinsulinism
  • Define the clinical features, and pathophysiology of congenital hyperinsulinism
  • Develop the best approaches to diagnose congenital hyperinsulinism
  • Use congenital hyperinsulinism to understand physiology and broader concepts
  • Understand the relationship between hyperinsulinism and other related disorders of insulin secretion.
NameRole
Professor Sarah Flanagan Associate Professor of Genomic Medicine, Wellcome Trust/Royal Society Sir Henry Dale Fellow
Dr Matthew Wakeling Independent Research Fellow
Dr Thomas Laver Lecturer in Diabetes
Dr Kashyap Patel Wellcome Trust Career Development Fellow, Honorary Consultant in Diabetes & Endocrinology
Dr Kevin Colclough Clinical Scientist, Joint head NHS MODY genetic testing service
Dr Jayne Houghton Clinical Scientist, Joint head NHS MODY genetic testing service
Dr Rachel van Heugten Healthcare Scientist 
Dr Ana Moleirhino Healthcare Scientist
Tom Hewat PhD Student
Jasmin Hopkins PhD Student
Eleanor Self Research Assistant

Key publications

Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2

Cabezas OR, Flanagan SE, Stanescu H, García-Martínez E, Caswell R, Lango-Allen H, Antón-Gamero M, Argente J, Bussell AM, Brandli A, Cheshire C, Crowne E, Dumitriu S, Drynda R, Hamilton-Shield JP, Hayes W, Hofherr A, Iancu D, Issler N, Jefferies C, Jones P, Johnson M, Kesselheim A, Klootwijk E, Koettgen M, Lewis W, Martos JM, Mozere M, Norman J, Patel V, Parrish A, Pérez-Cerdá C, Pozo J, Rahman SA, Sebire N, Tekman M, Turnpenny PD, Hoff WV, Viering DHHM, Weedon MN, Wilson P, Guay-Woodford L, Kleta R, Hussain K, Ellard S, Bockenhauer D..

J Am Soc Nephrol. 2017 Aug;28(8):2529-2539.

A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia

Flanagan SE, Vairo F, Johnson MB, Caswell R, Laver TW, Lango Allen H, Hussain K, Ellard S.

Pediatr Diabetes. 2017 Jun;18(4):320-323.

Next-Generation Sequencing Reveals Deep Intronic Cryptic ABCC8 and HADH Splicing Founder Mutations Causing Hyperinsulinism by Pseudoexon Activation

Flanagan SE, Xie W, Caswell R, Damhuis A, Vianey-Saban C, Akcay T, Darendeliler F, Bas F, Guven A, Siklar Z, Ocal G, Berberoglu M, Murphy N, O'Sullivan M, Green A, Clayton PE, Banerjee I, Clayton PT, Hussain K, Weedon MN, Ellard S.

Am J Hum Genet. 2013 10;92(1):131-6

Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome

Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, Splitt M, Berbero─člu M, Empting S, Wabitsch M, Pötzsch S, Shah P, Siklar Z, Verge CF, Weedon MN, Ellard S, Hussain K, Flanagan SE.

Wellcome Open Res. 2019 Oct 8;4:149.

Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389

Yau D, Laver TW, Dastamani A, Senniappan S, Houghton JAL, Shaikh G, Cheetham T, Mushtaq T, Kapoor RR, Randell T, Ellard S, Shah P, Banerjee I, Flanagan SE.

PLoS One. 2020 Feb 6;15(2) 

MAFA missense mutation causes familial insulinomatosis and diabetes mellitus

Iacovazzo D, Flanagan SE, Walker E, Quezado R, de Sousa Barros FA, Caswell R, Johnson MB, Wakeling M, Brändle M, Guo M, Dang MN, Gabrovska P, Niederle B, Christ E, Jenni S, Sipos B, Nieser M, Frilling A, Dhatariya K, Chanson P, de Herder WW, Konukiewitz B, Klöppel G, Stein R, Korbonits M, Ellard S.

Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1027-1032

The group has active collaborations with:

  • University of Manchester
  • Manchester Children’s Hospital
  • Great Ormond Street Hospital for Children
  • Imperial College London
  • Hôpital Universitaire Necker Enfants Malades, Paris, France
  • University of Chicago, USA
  • Stanford University, USA
  • Congenital Hyperinsulinism International, USA

The group's funders include: The Wellcome Trust, Royal Society, Diabetes UK and Congenital Hyperinsulinism International.

The Hyperinsulinism research group uses the following research facilities and technologies:

  • The Exeter Sequencing Service
  • RILD Molecular Biology Resources
  • High Performance Computing

More details of all of these can be found here.