Hyperinsulinism Genes Exeter

University of Exeter Medical School, Exeter, UK

info@hyperinsulinismgenes.org

Our Publications

We are a leading contributor to Congenital Hyperinsulinism research, with over 110 published papers produced in collaboration with international teams.

Featured Publications – Top 10 Papers

Our research has shaped the understanding, diagnosis, and treatment of congenital hyperinsulinism. The ten papers highlighted below have been published in high impact journals like Nature Genetics and PNAS and represent some of the most influential studies from our team. These papers showcase advances in the understanding of gene regulation, patient care, and population-level understanding of HI.

Each entry includes a Technical summary for clinicians and researchers, as well as a Plain English summary for families and non-specialist readers.

📊 Epidemiology | Global Incidence

Yau D, Laver TW, Dastamani A, et al. (2020)
Using referral rates for genetic testing to determine the incidence of congenital hyperinsulinism worldwide. PLOS ONE 15(2):e0228417

📊 Citations: ~60+
🔗 View Paper

Technical summary
We used national genetic testing referral data to calculate the incidence of congenital hyperinsulinism, finding approximately 1 in 28,389 live births in the UK. The study provides critical population-level data that inform healthcare planning and the epidemiology of HI.

Plain English summary
By analysing genetic testing referrals, we estimated how common congenital hyperinsulinism is in newborns. Knowing approximate incidence helps hospitals prepare services and supports families seeking context about rarity and risk.

🧬 Genetics | Regulatory DNA

Wakeling MN, Owens NDL, Hopkinson JR, et al. (2022)
Non‑coding variants disrupting a tissue‑specific regulatory element in HK1 cause congenital hyperinsulinism. Nature Genetics 54:1615–1620

📊 Citations: ~61+
🔗 View Paper

Technical summary
In this study we identified non-coding regulatory variants in HK1 that disrupt β-cell-specific gene silencing, causing congenital hyperinsulinism. It demonstrated that gene regulation defects outside coding regions can lead to disease, expanding diagnostic strategies for unexplained cases.

Plain English summary
This research showed that DNA changes outside genes can still trigger hyperinsulinism by turning on insulin production when it shouldn’t happen, explaining more cases that standard tests missed.

🧬 Genetics | Disease Severity

Bennett JJ, Saint‑Martin C, Neumann B, et al. (2025)
Non‑coding cis‑regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity. Genome Medicine 17:17

📊 Citations: emerging
🔗 View Paper

Technical summary
In this study we quantified how cis-regulatory HK1 variants contribute to previously unexplained HI and demonstrated that they are associated with variable disease severity. It refined genotype–phenotype correlations and informed clinical expectations.

Plain English summary
The same type of genetic change can cause mild or severe symptoms in different children, helping families understand why reactions to the condition vary so much.

🧬 Structural Variants | Pancreatic Development

Laver TW, Wakeling MN, Caswell RC, et al. (2024)
Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or regulatory elements. European Journal of Human Genetics 32:813–818

📊 Citations: emerging
🔗 View Paper

Technical summary
Chromosomal deletions of 20p11.2 affecting FOXA2 or its regulatory elements impair pancreatic development, resulting in HI. In this study we expanded the genetic architecture of HI to include structural and regulatory variation.

Plain English summary
This research showed that missing pieces of a chromosome can affect how the pancreas develops and controls insulin, helping explain rare genetic causes of HI.

🧬 Core Disease Genes | Reference Resource

Flanagan SE, Clauin S, Bellanné‑Chantelot C, et al. (2009)
Update of mutations in the genes encoding the pancreatic β‑cell K(ATP) channel subunits KCNJ11 and ABCC8 in diabetes mellitus and hyperinsulinism. Human Mutation 30(2):170–180

📊 Citations: ~182+
🔗 View Paper

Technical summary
In this comprehensive mutation update we catalogued pathogenic variants in K-ATP channel genes and linked them to clinical phenotypes across diabetes and hyperinsulinism. It remains a key resource for clinical genetics and variant interpretation.

Plain English summary
This review brought together information on the most common gene causes of HI and helped clinicians and labs decide which DNA changes are important.

🧬 Hidden Variants| Advanced Genomics

Flanagan SE, Xie W, Caswell R, et al. (2013)
Next‑Generation Sequencing Reveals Deep Intronic Cryptic ABCC8 and HADH Splicing Founder Mutations Causing Hyperinsulinism. American Journal of Human Genetics 92(1):131–136

📊 Citations: ~99+
🔗 View Paper

Technical summary
Using next-generation sequencing we identified deep intronic mutations activating cryptic splice sites in ABCC8 and HADH, solving previously unexplained cases. It emphasized the importance of non-coding regions in diagnosing HI.

Plain English summary
The work found hidden genetic changes that standard tests missed, explaining more cases and improving genetic diagnosis.

🏥 Clinical Cohort | Natural History

Kapoor RR, Flanagan SE, Arya VB, et al. (2013)
Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. European Journal of Endocrinology 168(4):557–564

📊 Citations: ~276+
🔗 View Paper

Technical summary
A cohort study of 300 patients detailing genetic causes, clinical features, and treatment responses. The study informed diagnostic pathways and modern management strategies for HI.

Plain English summary
By studying many children, this research showed how varied HI can be and what treatments work best, helping families set realistic expectations.

🧬 Gene–Phenotype Relationships | Birthweight

Pearson ER, Boj SF, Steele AM, et al. (2007)
Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous HNF4A mutations. PLoS Medicine 4(4):e118

📊 Citations: ~200+
🔗 View Paper

Technical summary
The first description of heterozygous HNF4A variants causing increased birthweight and neonatal hyperinsulinaemic hypoglycaemia, also highlighting later diabetes risk.

Plain English summary
The study showed that babies with certain gene changes are larger at birth and may develop low blood sugar soon after, giving families insight into genetic causes of HI.

💊 Treatment | Precision Medicine

Flanagan SE, Kapoor RR, Mali G, et al. (2010)
Diazoxide‑responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. European Journal of Endocrinology 162(5):987–992

📊 Citations: ~170+
🔗 View Paper

Technical summary
HNF4A-related hyperinsulinism often responds to diazoxide therapy. The study supports genotype-guided treatment decisions, minimizing the need for surgery.

Plain English summary
Knowing the genetic cause can help doctors choose effective medication and avoid unnecessary surgery.

🧬 Transcription Factors | Tumour Biology

Iacovazzo D, Flanagan SE, et al. (2018)
MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. PNAS 115(5):1027–1032

📊 Citations: ~133+
🔗 View Paper

Technical summary
A MAFA missense variant was linked to familial insulin-secreting tumours and diabetes, revealing a new mechanism for insulin dysregulation and benign endocrine tumor risk.

Plain English summary
It explained why some families develop both insulin-secreting tumours and diabetes, uncovering a new gene involved in insulin control.

117 studies published since 2008

Genetic Discovery

  1. Laver TW et al. Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements. Eur J Hum Genet. 2024 Jul;32(7):813-818. doi: 10.1038/s41431-024-01593-z. PMID: 38605124.
  2. Wakeling MN et al. Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism. Nat Genet. 2022;54:1615-1620. doi: 10.1038/s41588-022-01204-x. PMID: 36333503.
  3. Iacovazzo D, Flanagan SE, et al. MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1027-1032.
  4. Banerjee I et al. Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome. Wellcome Open Res. 2020 Aug 4;4:149. doi: 10.12688/wellcomeopenres.15465.2. eCollection 2019. PMID: 32832699
  5. Kostopoulou E, et al. Hyperinsulinaemic hypoglycaemia: A new presentation of 16p11.2 deletion syndrome. Clin Endocrinol (Oxf). 2019 May;90(5):766-769
  6. Laver TW et al. Analysis of large-scale sequencing cohorts does not support the role of variants in UCP2 as a cause of hyperinsulinaemic hypoglycaemia. Hum Mutat. 2017 Oct;38(10):1442-1444.
  7. Cabezas OR et al. Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. J Am Soc Nephrol. 2017 Aug;28(8):2529-2539.
  8. Flanagan SE et al. A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatr Diabetes. 2017 Jun;18(4):320-323
  9. Flanagan SE et al. Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: expanding the clinical phenotype. 2013 56(1):218-21
  10. Flanagan SE et al. Paternal Uniparental Isodisomy of Chromosome 11p15.5 within the Pancreas Causes Isolated Hyperinsulinemic Hypoglycemia. Front Endocrinol (Lausanne). 2011;2:66.
  11. Flanagan S et al. Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia. Pediatr Diabetes. 2012 13:285-9.
  12. Flanagan SE et al. Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia. Clin Genet. 2011 79(6):582-7

Screening Strategies

  1. Männistö JME, Houghton JAL, Bennett JJ, Keskinen P, Tuomi T, Ruuskanen H, Viikari LA, Jokiniitty A, Lähde J, Raivo J, Otonkoski T, Huopio H, Flanagan SE. Comprehensive genetic rescreening improves diagnostic yield in congenital hyperinsulinism. J Endocr Soc. 2026 Mar 3;10(4):bvag047. doi:10.1210/jendso/bvag047. PMID: 41924297; PMCID: PMC13035452.
  2. Flanagan SE et al . Large copy number variants are an important cause of congenital hyperinsulinism that should be screened for during routine testing. Front Endocrinol (Lausanne). 2025 Feb 18;16:1514916. doi:10.3389/fendo.2025.1514916. PMID: 40041288; PMCID: PMC11876054.
  3. Hopkins JJ et al. Hyperinsulinaemic hypoglycaemia diagnosed in childhood can be monogenic. J Clin Endocrinol Metab. 2023 15;108(3):680-687. doi:10.1210/clinem/dgac604. PMID: 36239000; PMCID: PMC9931180.
  4. Hewat TI et al. Congenital Hyperinsulinism: Current Laboratory-Based Approaches to the Genetic Diagnosis of a Heterogeneous Disease. Front Endocrinol (Lausanne). 2022 Jul 7; 13:873254. doi:10.3389/fendo.2022.873254. PMID: 35872984; PMCID: PMC9302115.
  5. Hewat TI et al. Birth weight and diazoxide unresponsiveness strongly predict the likelihood of congenital hyperinsulinism due to a mutation in ABCC8 or KCNJ11. Eur J Endocrinol. 2021 Oct 1:EJE-21-0476.doi: 10.1530/EJE-21-0476. PMID: 34633981.
  6. Laver TW et al. Comprehensive screening shows that mutations in the known syndromic genes are rare in infants presenting with hyperinsulinaemic hypoglycaemia. Clin Endocrinol (Oxf). 2018 89(5):621-627.
  7. Arya VB et al. Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age. Arch Dis Child Fetal Neonatal Ed. 2013 98(4):F356-8.

Improved Detection and Interpretation of Genetic Variation

  1. Laver TW, Sangha P, Mallin L, Cohen M, Ünsal Y, Demirbilek H, Wakeling MN, Bennett JJ, Houghton JAL, Männistö JME, Dempster E, Flanagan SE. Long-read sequencing enables trio-assisted phasing of de novo variants in the imprinted gene MAGEL2. J Med Genet. 2026 Mar 31:jmg-2025-111282. doi: 10.1136/jmg-2025-111282. Epub ahead of print. PMID: 41916724.
  2. Männistö JME et al. Congenital hyperinsulinism and novel KDM6A duplications – resolving pathogenicity with genome and epigenetic analyses. J Clin Endocrinol Metab. 2024. doi: 10.1210/clinem/dgae524. PMID: 39078990.
  3. Hewat TI et al. Increased referrals for congenital hyperinsulinism genetic testing in children with trisomy 21 reflects the high burden of non-genetic risk factors in this group. Pediatr Diabetes. 2022 Mar 16. doi: 10.1111/pedi.13333. Epub ahead of print. PMID: 35294086.
  4. Hopkins JJ et al. REVEL Is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants Human Mutation, vol. 2023, Article ID 8857940, 2023.https://doi.org/10.1155/2023/8857940
  5. Wakeling MN et al. Homozygosity mapping provides supporting evidence of pathogenicity in recessive Mendelian disease. Genet Med. 2019 Apr;21(4):982-986
  6. Flanagan SE et al. Next-Generation Sequencing Reveals Deep Intronic Cryptic ABCC8 and HADH Splicing Founder Mutations Causing Hyperinsulinism by Pseudoexon Activation. Am J Hum Genet. 2013 10;92(1):131-6
  7. Flanagan SE et al. Using SIFT and PolyPhen to Predict Loss-of-Function and Gain-of-Function Mutations. Genet Test Mol Biomarkers. 2010 14(4):533-7.

Syndromic Forms of Hyperinsulinism

  1. Ibeas C, Giraudo F, Männistö JME, Flanagan SE, Mericq V. Congenital hyperinsulinism in an individual with CHARGE syndrome and a pathogenic CHD7 variant. JCEM Case Rep. 2026 24;4(3):doi:10.1210/jcemcr/luag016. PMID: 41743177; PMCID: PMC12930190.

Correlating Genetics with Histology

  1. Houghton JAL et al. Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism. J Pathol Clin Res. 2020;6:12-16.
  2. Craigie RJ et al. Clinical Diversity in Focal Congenital Hyperinsulinism in Infancy Correlates With Histological Heterogeneity of Islet Cell Lesions. Front Endocrinol (Lausanne). 2018 Oct 17;9:619.
  3. Han B et al. Atypical Forms of Congenital Hyperinsulinism In Infancy are Associated with Mosaic Patterns of Immature Islet Cells. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3261-3267
  4. Ismail D et al. The Heterogeneity of Focal Forms of Congenital Hyperinsulinism. J Clin Endocrinol Metab. 2012 Jan;97(1):E94-9
  5. Hussain K et al. An ABCC8 gene mutation and mosaic uniparental isodisomy resulting in atypical diffuse congenital hyperinsulinism. Diabetes. 2008; 57(1):259-63

Treatment and Surgical Outcomes

  1. Karlekar MP et al. Octreotide-LAR is a Useful Alternative for the Management of Diazoxide-Responsive Congenital Hyperinsulinism. Horm Metab Res. 2021 Nov;53(11):723-729. doi: 10.1055/a-1654-8542. Epub 2021 Nov 5. PMID: 34740273.
  2. Arya VB et al Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation. Endocrinol Diabetes Metab Case Rep. 2019
  3. Guemes M et al. Efficacy and Complications in Children With Hyperinsulinemic Hypoglycemia: A 5-Year Follow-Up Study. J Endocr Soc. 2019 Feb 7;3(4):699-713.
  4. Salomon-Estebanez M et al. Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time. Orphanet J Rare Dis. 2016 Dec 1;11(1):163.
  5. Mangla P et al. Diazoxide toxicity in a child with persistent hyperinsulinemic hypoglycemia of infancy: mixed hyperglycemic hyperosmolar coma and ketoacidosis. J Pediatr Endocrinol Metab. 2018 Aug 28;31(8):943-945.
  6. Haliloğlu B et al. Sirolimus-Induced Hepatitis in Two Patients with Hyperinsulinemic Hypoglycemia. J Clin Res Pediatr Endocrinol. 2018 Jul 31;10(3):279-283.
  7. Khawash P et al. Nifedipine in Congenital Hyperinsulinism-A Case Report. J Clin Res Pediatr Endocrinol. 2015 Jun 5;7(2):151-4.
  8. Abraham MB et al. Efficacy and safety of sirolimus in a neonate with persistent hypoglycaemia following near-total pancreatectomy for hyperinsulinaemic hypoglycaemia. J Pediatr Endocrinol Metab. 2015 Nov 1;28(11-12):1391-8.
  9. Demirbilek H et al. Long-term follow up of Children with Congenital Hyperinsulinism on Octreotide Therapy. J Clin Endocrinol Metab. 2014 Oct;99(10):3660-7.
  10. Durmaz E et al. A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycaemic infant. J Clin Res Pediatr Endocrinol. 2014 Jun 5;6(2):119-21.
  11. Arya VB et al. Pancreatic Endocrine and Exocrine Function in Children following Near-Total Pancreatectomy for Diffuse Congenital Hyperinsulinism. PLoS One. 2014 19;9(5):e98054.
  12. Senniappan S et al. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med. 2014 20;370(12):1131-7.

Clinical Observations

  1. Shi Y et al. Increased Plasma Incretin Concentrations Identifies a Subset of Patients with Persistent Congenital Hyperinsulinism without K(ATP) Channel Gene Defects. J Pediatr. 2015 Jan;166(1):191-4.
  2. Banerjee I et al. The association of cardiac ventricular hypertrophy with Congenital Hyperinsulinism (CHI). Eur J 2012 167(5):619-24
  3. Heslegrave AJ et al. Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase.Orphanet J Rare Dis. 2012 14;7(1):25.
  4. Banerjee I et al. The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with Congenital Hyperinsulinism (CHI). Eur J Endocrinol. 2011 164(5):733-740.

Neurodevelopmental Outcomes

  1. Bowman P, Männistö JME, Flanagan SE. The effect of hypoglycaemia on neurodevelopment: insights from congenital hyperinsulinism. Nat Rev Endocrinol. 2026 Apr 16. doi: 10.1038/s41574-026-01253-w. Epub ahead of print. PMID:41991771.
  2. Aftab S et al. Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1. Endocr Connect. 2022 Aug 1:EC-22-0008. doi:10.1530/EC-22-0008. PMID: 35951311.

Cohort Studies

  1. Bennett JJ et al. Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity. Genome Med. 2025;17:17. doi: 10.1186/s13073-025-01440-w. PMID: 40033430.
  2. Pacheco G et al. Characterization of congenital hyperinsulinism in Argentina: Clinical features, genetic findings, and treatment outcomes. PLoS One. 2025 20(8):e0321244. doi: 10.1371/journal.pone.0321244. PMID: 40828772
  3. Abali Z et al. Comprehensive clinical and molecular characterization with long-term outcomes in 40 patients with congenital hyperinsulinism. Endocrine. 2025 Aug;89(2):416-428. doi: 10.1007/s12020-025-04244-5. Epub 2025 May 18. PMID:40382736.
  4. Globa E et al. Congenital hyperinsulinism in the Ukraine: a 10-year national study. Front Endocrinol (Lausanne). 2024;15:1497579. doi: 10.3389/fendo.2024.1497579. PMID: 39741883.
  5. Navasardyan LV et al. Congenital Hyperinsulinism: First case reports from the Republic of Armenia; The New Armenian Medical Journal, 2024 18(2), p.128-131; DOI: https://doi.org/ 10.56936/18290825-2.v18.2024-128
  6. Dastamani A et al. Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism-The UK Perspective. J Endocr Soc. 2022 Mar 15;6(6) bvac033. doi:10.1210/jendso/bvac033. PMID: 35592516; PMCID: PMC9113085.
  7. McGlacken-Byrne SM et al. Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia. Eur J Endocrinol. 2022 Feb 22;186(4):417-427. doi: 10.1530/EJE-21-0897. PMID: 35089870.
  8. Sharma R et al. Molecular Characterization and Management of Congenital Hyperinsulinism: A Tertiary Centre Experience. Indian Pediatr. 2022 Jan 5:S097475591600386. Epub ahead of print. PMID: 34992182.
  9. Sethi et al. Heterozygous Insulin Receptor (INSR) Mutation associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series. J Clin Res Pediatr Endocrinol. 2020 Jan 28. doi:10.4274/jcrpe.galenos.2019.2019.0106. PubMed PMID:31989990.
  10. Roy K et al. Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1. Indian J Pediatr. 2019 Nov;86(11):1051-1053
  11. Güven A et al. Clinical, genetic characteristics, management and long-term follow up of Turkish patients with congenital hyperinsulinism. J Clin Res Pediatr Endocrinol. 2016 Jun 5;8(2):197-204.
  12. Senniappan S et al. Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia. BMC Res Notes. 2015 13;8:350.
  13. Arya VB et al Clinical and Histological Heterogeneity of Congenital Hyperinsulinism due to Paternally Inherited Heterozygous ABCC8/KCNJ11 Mutations. Eur J Endocrinol. 2014 Dec;171(6):685-95.
  14. Demirbilek H et al. Clinical characteristics and phenotype-genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations Eur J Endocrinol. 2014 170(6):885-92
  15. Simşek E et al. Congenital hyperinsulinism presenting with different clinical, biochemical and molecular genetic spectra. Turk J Pediatr. 2013 55(6):584-590.
  16. McGlacken-Byrne SM, Hawkes CP, Flanagan SE, Ellard S, McDonnell CM, Murphy NP. The evolving course of HNF4A hyperinsulinaemic hypoglycaemia-a case series. Diabet Med. 2014 31(1):e1-5
  17. Kapoor RR et al. Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. Eur J Endocrinol. 2013 15;168(4):557-64.
  18. Oçal G et al. Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potassium channel in the pancreatic beta cell. J Pediatr Endocrinol Metab. 2011;24(11-12):1019-23.
  19. Thakur S et al. Congenital Hyperinsulinism Caused by Mutations in ABCC8 (SUR1) Gene. Indian Pediatr. 2011 8;48(9):733-4.
  20. Kapoor RR et al. Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations. Diabetologia. 2011 54(10):2575-83.
  21. Park SE et al. Characterization of ABCC8 and KCNJ11 gene mutations and phenotypes in Korean patients with congenital hyperinsulinism. Eur J Endocrinol. 2011 164(6):919-926.
  22. Flanagan SE et al. Genome-Wide Homozygosity Analysis Reveals HADH Mutations as a Common Cause of Diazoxide-Responsive Hyperinsulinemic-Hypoglycemia in Consanguineous Pedigrees. J Clin Endocrinol Metab. 2011 96(3): e498-502.
  23. Flanagan SE et al. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol. 2010; 162(5):987-92.
  24. Kapoor RR et al. Hyperinsulinism-hyperammonaemia (HI/HA) syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations. Eur J Endocrinol. 2009;161(5):731-735.

Case Reports

  1. Kiff S et al. Partial diazoxide responsiveness in a neonate with hyperinsulinism due to homozygous ABCC8 mutation. Endocrinol Diabetes Metab Case Rep. 2019 [Epub ahead of print]
  2. Apperley L et al. A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8. J Pediatr Endocrinol Metab. 2019 Mar 26;32(3):301-304.
  3. Işık E et al Congenital Hyperinsulinism and Evolution to Sulfonylurea responsive Diabetes Later in Life due to a Novel Homozygous p.L171F ABCC8 Mutation. J Clin Res Pediatr Endocrinol. 2019 Feb 20;11(1):82-87.
  4. Chinoy A et al. Focal Congenital Hyperinsulinism as a Cause for Sudden Infant Death. Pediatr Dev Pathol. 2019 Jan-Feb;22(1):65-69.
  5. Galcheva S et al. Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation. J Pediatr Endocrinol Metab. 2017 Apr 1;30(4):471-474.
  6. Bala KA et al. Congenital Hyperinsulinism: A novel mutation in the KCNJ11 gene. J Pancreas 2017 March 30: 18(2):151-153
  7. Satapathy AK et al. Hyperinsulinemic Hypoglycemia of Infancy due to Novel HADH Mutation in Two Siblings. Indian Pediatr. 2016 Oct 8;53(10):912-913
  8. Ünal S et al. A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus. J Clin Res Pediatr Endocrinol. 2016 1;8(4):478-481.
  9. Kocaay P et al. Coexistence of Mosaic Uniparental Isodisomy and a KCNJ11 Mutation Presenting as Diffuse Congenital Hyperinsulinism and Hemihypertrophy. Horm Res Paediatr. 2016;85(6):421-5
  10. Çamtosun E et al A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course. J Clin Res Pediatr Endocrinol. 2015 5;7(2):144-7.
  11. Babiker O et al. Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family. J Pediatr Endocrinol Metab. 2015 Sep;28(9-10):1073-7.
  12. Harel S et al. Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture. J Pediatr Endocrinol Metab. 2015 Mar;28(3-4):345-51.
  13. Shah P et al. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation.J Pediatr Endocrinol Metab. 2015 May;28(5-6):695-9
  14. Kocaay P et al. Coexistence of Mosaic Uniparental Isodisomy and a KCNJ11 Mutation Presenting as Diffuse Congenital Hyperinsulinism and Hemihypertrophy. Horm Res Paediatr. 2016;85(6):421-5
  15. Çamtosun E et al. A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course. J Clin Res Pediatr Endocrinol. 2015 5;7(2):144-7.
  16. Babiker O et al. Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family. J Pediatr Endocrinol Metab. 2015 Sep;28(9-10):1073-7.
  17. Harel S et al. Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture. J Pediatr Endocrinol Metab. 2015 Mar;28(3-4):345-51.
  18. Shah P et al. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation.J Pediatr Endocrinol Metab. 2015 May;28(5-6):695-9
  19. Ince DA et al. Congenital hyperinsulinism in a newborn with a novel homozygous mutation (p.Q392H) in the ABCC8 gene. J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1253-5.
  20. Kalaivanan P et al. Chromosome 6q24 transient neonatal diabetes mellitus and protein sensitive hyperinsulinaemic hypoglycaemia. J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1065-9.
  21. Arya VB et al. HNF4A mutation: switch from hyperinsulinaemic hypoglycaemia to maturity-onset diabetes of the young, and incretin response. Diabet Med. 2014 31(3):e11-5
  22. Arya VB et al. Activating AKT2 mutation: Hypoinsulinaemic hypoketotic hypoglycaemia. J Clin Endocrinol Metab. 2013 99(2):391-4
  23. Khoriati D et al. Prematurity, macrosomia, hyperinsulinaemic hypoglycaemia and a dominant ABCC8 gene mutation. BMJ Case Rep. 2013 5;2013
  24. Bayarchimeg M et al. Galactokinase deficiency in a patient with congenital hyperinsulinism. JIMD Rep. 2012;5:7-11.
  25. Chandran S et al. Paternally inherited ABCC8 mutation causing diffuse congenital hyperinsulinism. Endocrinol Diabetes Metab Case Rep. 2013;130041.
  26. Calton EA et al. Hepatoblastoma in a child with a paternally-inherited ABCC8 mutation and mosaic paternal uniparental disomy 11p causing focal congenital hyperinsulinism. Eur J Med 2013 56(2):114-7
  27. Balasubramaniam S et al. Biochemical evaluation of an infant with hypoglycemia resulting from a novel de novo mutation of the GLUD1 gene and hyperinsulinism-hyperammonemia syndrome. J Pediatr Endocrinol Metab. 2011;24(7-8):573-7.
  28. Kapoor RR et al. Congenital hyperinsulinism: Marked clinical heterogeneity in siblings with identical mutations in the ABCC8 gene. Clin Endocrinol (Oxf). 2012 76(2):312-3
  29. Ismail D et al. Familial Focal Congenital Hyperinsulinism. JCEM. 2011 96(1):24-8.
  30. Padidela R et al. Focal congenital hyperinsulinism in a patient with septo-optic dysplasia. Nat Rev Endocrinol. 2010 6(11):646-50.
  31. Kumaran A et al. Congenital Hyperinsulinism due to a Compound Heterozygous ABCC8 Mutation with Spontaneous Resolution at Eight Weeks. Horm Res Paediatr. 2010;73(4):287-292.
  32. Kapoor RR et al. 3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency and Hyperinsulinaemic Hypoglycaemia: Characterization of a Novel Mutation and Severe Dietary Protein Sensitivity. JCEM 2009 94(7):2221-5.

Population-specific genetics and founder variants

  1. Jain V et al. The p.(Gly111Arg) ABCC8 Variant: A Founder Mutation in the Indian Agarwal Community. Clin Genet. 2025;107:364-365. doi: 10.1111/cge.14657. PMID: 39601258.
  2. Islam S et al. Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD). Mol Genet Genomic Med. 2021 Dec;9(12) e1674. doi: 10.1002/mgg3.1674. PMID: 33811480; PMCID: PMC8683636.
  3. Flanagan SE et al. Next-Generation Sequencing Reveals Deep Intronic Cryptic ABCC8 and HADH Splicing Founder Mutations Causing Hyperinsulinism by Pseudoexon Activation. Am J Hum Genet. 2013 10;92(1):131-6

Prevalence studies

  1. Yau D et al. Using referral rates for genetic testing to determine the incidence of a rare disease: CHI incidence in the UK is 1 in 28,389. PLoS One. 2020;15:e0228417. doi: 10.1371/journal.pone.0228417. PMID: 32027664.

Functional biology studies

  1. Walker EM et al. Sex-biased islet β cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males. Cell Rep. 2021 12;37(2):109813. doi:10.1016/j.celrep.2021.109813. PMID: 34644565.
  2. Männikkö R et al. Mutations of the Same Conserved Glutamate Residue in NBD2 of the Sulfonylurea Receptor 1 Subunit of the KATP Channel Can Result in Either Hyperinsulinism or Neonatal Diabetes. 2011 60(6):1813-22.
  3. Powell PD et al. In Vitro Recovery of ATP-Sensitive Potassium Channels in Beta Cells From Patients With Congenital Hyperinsulinism of Infancy. Diabetes. 2011 60(4):1223-8
  4. Shimomura K et al. Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism. EMBO Mol Med. 2009 1:166-177

Mutation Updates

  1. De Franco E et al. Update of variants identified in the pancreatic beta-cell K(ATP) channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes. Hum Mutat. 2020 May;41(5):884-905. doi: 10.1002/humu.23995. Epub 2020 Feb 17
  2. Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. Hum Mutat. 2013 34(5):669-85.
  3. Flanagan SE et al. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat. 2009;30(2):170-80

Software Development

  1. Laver TW et al. SavvyCNV: Genome-wide CNV calling from off-target reads. PLoS Comput Biol. 2022;18:e1009940. doi: 10.1371/journal.pcbi.1009940. PMID: 35294448.