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.

Hyperinsulinism - People

Name	Role
Professor Sarah Flanagan	Associate Professor of Genomic Medicine and Wellcome Trust Senior Research 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 Jessica Hopkinson	Post Doctoral Research Fellow
Jasmin Hopkins	PhD Student

Publications

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, Berberoğlu 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

Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism

Wakeling MN, Owens NDL, Hopkinson JR, Johnson MB, Houghton JAL, Dastamani A, Flaxman CS, Wyatt RC, Hewat TI, Hopkins JJ, Laver TW, van Heugten R, Weedon MN, De Franco E, Patel KA, Ellard S, Morgan NG, Cheesman E, Banerjee I, Hattersley AT, Dunne MJ; International Congenital Hyperinsulinism Consortium, Richardson SJ, Flanagan SE.

Nat Genet. 2022 Nov;54(11):1615-1620. doi: 10.1038/s41588-022-01204-x. Epub 2022 Nov 4. PMID: 36333503.

Collaborations

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

Funding

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

Facilities and Technologies used

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.