Insulin mutation screening in 1,044 patients with diabetes: Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood

Edghill, Emma L., Flanagan, Sarah E., Patch, Ann-Marie, Boustred, Chris, Parrish, Andrew, Shields, Beverley, Shepherd, Maggie H., Hussain, Khalid, Kapoor, Ritika R., Malecki, Maciej, MacDonald, Michael J., Støy, Julie, Steiner, Donald F., Philipson, Louis H., Bell, Graeme I., The Neonatal Diabetes International Collaborative Group, Hattersley, Andrew T. and Ellard, Sian (2008) Insulin mutation screening in 1,044 patients with diabetes: Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes, 57 4: 1034-1042. doi:10.2337/db07-1405


Author Edghill, Emma L.
Flanagan, Sarah E.
Patch, Ann-Marie
Boustred, Chris
Parrish, Andrew
Shields, Beverley
Shepherd, Maggie H.
Hussain, Khalid
Kapoor, Ritika R.
Malecki, Maciej
MacDonald, Michael J.
Støy, Julie
Steiner, Donald F.
Philipson, Louis H.
Bell, Graeme I.
The Neonatal Diabetes International Collaborative Group
Hattersley, Andrew T.
Ellard, Sian
Title Insulin mutation screening in 1,044 patients with diabetes: Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood
Formatted title
Insulin mutation screening in 1,044 patients with diabetes: Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
1939-327X
Publication date 2008-04
Year available 2007
Sub-type Article (original research)
DOI 10.2337/db07-1405
Volume 57
Issue 4
Start page 1034
End page 1042
Total pages 9
Place of publication Alexandria, VA, U.S.A.
Publisher American Diabetes Association
Language eng
Formatted abstract
OBJECTIVE— Insulin gene (INS) mutations have recently been described as a cause of permanent neonatal diabetes (PND). We aimed to determine the prevalence, genetics, and clinical phenotype of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, childhood, or adulthood.

RESEARCH DESIGN AND METHODS— The INS gene was sequenced in 285 patients with diabetes diagnosed before 2 years of age, 296 probands with maturity-onset diabetes of the young (MODY), and 463 patients with young-onset type 2 diabetes (nonobese, diagnosed <45 years). None had a molecular genetic diagnosis of monogenic diabetes.

RESULTS— We identified heterozygous INS mutations in 33 of 141 probands diagnosed at <6 months, 2 of 86 between 6 and 12 months, and none of 58 between 12 and 24 months of age. Three known mutations (A24D, F48C, and R89C) account for 46% of cases. There were six novel mutations: H29D, L35P, G84R, C96S, S101C, and Y103C. INS mutation carriers were all insulin treated from diagnosis and were diagnosed later than ATP-sensitive K+ channel mutation carriers (11 vs. 8 weeks, P < 0.01). In 279 patients with PND, the frequency of KCNJ11, ABCC8, and INS gene mutations was 31, 10, and 12%, respectively. A heterozygous R6C mutation cosegregated with diabetes in a MODY family and is probably pathogenic, but the L68M substitution identified in a patient with young-onset type 2 diabetes may be a rare nonfunctional variant.

CONCLUSIONS— We conclude that INS mutations are the second most common cause of PND and a rare cause of MODY. Insulin gene mutation screening is recommended for all diabetic patients diagnosed before 1 year of age.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Published ahead of print on 27 December 2007

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Thu, 05 May 2011, 11:47:31 EST by Susan Allen on behalf of Institute for Molecular Bioscience